International Journal of Molecular Sciences

Research

Jump to: Review, Other

16 pages, 2526 KiB

Open AccessArticle

Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics

by Bin Hu, Michael Rotherham, Neil Farrow, Paul Roach, Jon Dobson and Alicia J. El Haj

Int. J. Mol. Sci. 2022, 23(17), 10164; https://doi.org/10.3390/ijms231710164 - 5 Sep 2022

Cited by 5 | Viewed by 2186

Abstract

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/β-catenin signaling is linked to cancer. Therefore, technologies [...] Read more.

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/β-catenin signaling is linked to cancer. Therefore, technologies for local modulation and control of Wnt signaling targeted to specific sites of disease or degeneration have potential therapeutic value in the treatment of degenerative diseases. We reported a facile approach to locally activate the canonical Wnt signaling cascade using nanomagnetic actuation or ligand immobilized platforms. Using a human embryonic kidney (HEK293) Luc-TCF/LEF reporter cell line, we demonstrated that targeting the cell membrane Wnt receptor, Frizzled 2, with peptide-tagged magnetic nanoparticles (MNPs) triggered canonical Wnt signaling transduction when exposed to a high-gradient, time-varying magnetic field, and the induced TCF/LEF signal transduction was shown to be avidity-dependent. We also demonstrated that the peptide retained signaling activity after functionalization onto glass surfaces, providing a versatile platform for drug discovery or recreation of the cell niche. In conclusion, these results showed that peptide-mediated Wnt signaling kinetics depended not only on ligand concentration but also on the presentation method of the ligand, which may be further modulated by magnetic actuation. This has important implications when designing future therapeutic platforms involving Wnt mimetics. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

20 pages, 7106 KiB

Open AccessArticle

Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

by Huey-Shan Hung, Kai-Bo Chang, Cheng-Ming Tang, Tian-Ren Ku, Mei-Lang Kung, Alex Yang-Hao Yu, Chiung-Chyi Shen, Yi-Chin Yang, Hsien-Hsu Hsieh and Shan-hui Hsu

Int. J. Mol. Sci. 2021, 22(17), 9262; https://doi.org/10.3390/ijms22179262 - 26 Aug 2021

Cited by 8 | Viewed by 3526 | Correction

Abstract

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its [...] Read more.

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

10 pages, 2980 KiB

Open AccessArticle

One Pot Synthesis of Large Gold Nanoparticles with Triple Functional Ferrocene Ligands

by Shenqing Wang, Fang Liu, Yin Liu, Hongyu Zhou and Bing Yan

Int. J. Mol. Sci. 2021, 22(5), 2328; https://doi.org/10.3390/ijms22052328 - 26 Feb 2021

Cited by 3 | Viewed by 2982

Abstract

In biomedical, toxicological, and optoelectronic applications, the size of nanoparticles is one of the decisive factors. Therefore, synthesis of nanoparticles with controlled sizes is required. The current methods for synthesis of larger gold nanoparticles (GNPs, ~200 nm) are complex and tedious, producing nanoparticles [...] Read more.

In biomedical, toxicological, and optoelectronic applications, the size of nanoparticles is one of the decisive factors. Therefore, synthesis of nanoparticles with controlled sizes is required. The current methods for synthesis of larger gold nanoparticles (GNPs, ~200 nm) are complex and tedious, producing nanoparticles with a lower yield and more irregular shapes. Using ferrocene as a primary reducing agent and stabilizer, sodium citrate as a dispersant, and sodium borohydride as an accessory reducing agent, GNPs of 200 nm were synthesized in a one pot reaction. Besides the roles of reducing agent and GNP stabilizer, ferrocene also served a role of quantitative marker for ligand loading, allowing an accurate determinate of surface ligands. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

12 pages, 4420 KiB

Open AccessArticle

Boosting of Antibacterial Performance of Cellulose Based Paper Sheet via TiO₂ Nanoparticles

by Klaudia Maślana, Anna Żywicka, Karolina Wenelska and Ewa Mijowska

Int. J. Mol. Sci. 2021, 22(3), 1451; https://doi.org/10.3390/ijms22031451 - 1 Feb 2021

Cited by 17 | Viewed by 2902

Abstract

Here, we aimed to boost antibacterial performance of cellulose fibers for paper sheet application. Therefore, TiO₂ nanoparticles have been used with controlled loading onto the surface of the fibers. A simple and facile composite preparation route based on ultrasound and mechanical assisted [...] Read more.

Here, we aimed to boost antibacterial performance of cellulose fibers for paper sheet application. Therefore, TiO₂ nanoparticles have been used with controlled loading onto the surface of the fibers. A simple and facile composite preparation route based on ultrasound and mechanical assisted stirring has been developed. We tested cellulose paper enriched by TiO₂ from 1.0 wt% to 8.0 wt%, respectively. Antibacterial performance has been studied against Staphylococcus aureus and Escherichia coli bacteria. Studies showed that all composites exhibit significant capability to reduce living cells of S. aureus and E. coli bacteria at least 60%. The simplicity, low cost, and reproducibility of the prepared method indicates the potential to be scaled up for industrial applications. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

11 pages, 976 KiB

Open AccessArticle

Looking for the LOAEL or NOAEL Concentration of Nickel-Oxide Nanoparticles in a Long-Term Inhalation Exposure of Rats

by Boris A. Katsnelson, Ivan N. Chernyshov, Svetlana N. Solovyeva, Ilzira A. Minigalieva, Vladimir B. Gurvich, Irene E. Valamina, Oleg H. Makeyev, Renata R. Sahautdinova, Larisa I. Privalova, Anastasia E. Tsaregorodtseva, Artem V. Korotkov, Eugene A. Shuman, Vladimir G. Panov and Marina P. Sutunkova

Int. J. Mol. Sci. 2021, 22(1), 416; https://doi.org/10.3390/ijms22010416 - 3 Jan 2021

Cited by 6 | Viewed by 2753

Abstract

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m³ in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based [...] Read more.

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m³ in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based on the majority of the effects assessed, this kind of exposure may be considered as close to LOAEL (lowest observed adverse effect level), or even to NOAEL (no observed adverse effect level). At the same time, the experiment revealed genotoxic and allergic effects as early as in the first weeks of exposure, suggesting that these effects may have no threshold at all. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

14 pages, 4988 KiB

Open AccessArticle

Indocyanine Green Loaded Modified Mesoporous Silica Nanoparticles as an Effective Photothermal Nanoplatform

by Yiyu Wang, Chunqing Niu, Sisi Fan, Yuwei Li, Xiang Li, Yujun Dai, Jian Shi and Xinyu Wang

Int. J. Mol. Sci. 2020, 21(13), 4789; https://doi.org/10.3390/ijms21134789 - 6 Jul 2020

Cited by 18 | Viewed by 4020

Abstract

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO₂-NH₂ NPs). SiO₂-NH₂ [...] Read more.

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO₂-NH₂ NPs). SiO₂-NH₂ NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO₂ NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO₂ NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO₂-NH₂ NPs by electrostatic attraction to enable SiO₂-NH₂@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO₂-NH₂ was greatly increased compared to unmodified SiO₂, and the stability of ICG was also improved. Moreover, the SiO₂-NH₂@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO₂-NH₂@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

13 pages, 4295 KiB

Open AccessArticle

Combination with l-Menthol Enhances Transdermal Penetration of Indomethacin Solid Nanoparticles

by Noriaki Nagai, Fumihiko Ogata, Mizuki Yamaguchi, Yuya Fukuoka, Hiroko Otake, Yosuke Nakazawa and Naohito Kawasaki

Int. J. Mol. Sci. 2019, 20(15), 3644; https://doi.org/10.3390/ijms20153644 - 25 Jul 2019

Cited by 18 | Viewed by 4953

Abstract

This study designed the transdermal formulations containing indomethacin (IMC)—1% IMC was crushed with 0.5% methylcellulose and 5% 2-hydroxypropyl-β-cyclodextrin by the bead mill method, and the milled IMC was gelled with or without 2% l-menthol (a permeation enhancer) by Carbopol^® 934 (without menthol, [...] Read more.

This study designed the transdermal formulations containing indomethacin (IMC)—1% IMC was crushed with 0.5% methylcellulose and 5% 2-hydroxypropyl-β-cyclodextrin by the bead mill method, and the milled IMC was gelled with or without 2% l-menthol (a permeation enhancer) by Carbopol^® 934 (without menthol, N-IMC gel; with menthol, N-IMC/MT gel). In addition, the drug release, skin penetration and percutaneous absorption of the N-IMC/MT gel were investigated. The particle sizes of N-IMC gel were approximately 50–200 nm, and the combination with l-menthol did not affect the particle characterization of the transdermal formulations. In an in vitro experiment using a Franz diffusion cell, the skin penetration in N-IMC/MT gel was enhanced than the N-IMC gel, and the percutaneous absorption (AUC) from the N-IMC/MT gel was 2-fold higher than the N-IMC gel. On the other hand, the skin penetration from the N-IMC/MT gel was remarkably attenuated at a 4 °C condition, a temperature that inhibits all energy-dependent endocytosis. In conclusion, this study designed transdermal formulations containing IMC solid nanoparticles and l-menthol, and found that the combination with l-menthol enhanced the skin penetration of the IMC solid nanoparticles. In addition, the energy-dependency of the skin penetration of IMC solid nanoparticles was demonstrated. These findings suggest the utility of a transdermal drug delivery system to provide the easy application of solid nanoparticles (SNPs). Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

22 pages, 8488 KiB

Open AccessArticle

Transformation of Construction Cement to a Self-Healing Hybrid Binder

by Werner E.G. Müller, Emad Tolba, Shunfeng Wang, Qiang Li, Meik Neufurth, Maximilian Ackermann, Rafael Muñoz-Espí, Heinz C. Schröder and Xiaohong Wang

Int. J. Mol. Sci. 2019, 20(12), 2948; https://doi.org/10.3390/ijms20122948 - 17 Jun 2019

Cited by 3 | Viewed by 4600

Abstract

A new biomimetic strategy to im prove the self-healing properties of Portland cement is presented that is based on the application of the biogenic inorganic polymer polyphosphate (polyP), which is used as a cement admixture. The data show that synthetic linear polyp, with [...] Read more.

A new biomimetic strategy to im prove the self-healing properties of Portland cement is presented that is based on the application of the biogenic inorganic polymer polyphosphate (polyP), which is used as a cement admixture. The data show that synthetic linear polyp, with an average chain length of 40, as well as natural long-chain polyP isolated from soil bacteria, has the ability to support self-healing of this construction material. Furthermore, polyP, used as a water-soluble Na-salt, is subject to Na⁺/Ca²⁺ exchange by the Ca²⁺ from the cement, resulting in the formation of a water-rich coacervate when added to the cement surface, especially to the surface of bacteria-containing cement/concrete samples. The addition of polyP in low concentrations (<1% on weight basis for the solids) not only accelerated the hardening of cement/concrete but also the healing of microcracks present in the material. The results suggest that long-chain polyP is a promising additive that increases the self-healing capacity of cement by mimicking a bacteria-mediated natural mechanism. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

24 pages, 6099 KiB

Open AccessArticle

Toxic Effects of Low-Level Long-Term Inhalation Exposures of Rats to Nickel Oxide Nanoparticles

by Marina P. Sutunkova, Svetlana N. Solovyeva, Ilzira A. Minigalieva, Vladimir B. Gurvich, Irene E. Valamina, Oleg H. Makeyev, Vladimir Ya. Shur, Ekaterina V. Shishkina, Ilya V. Zubarev, Renata R. Saatkhudinova, Svetlana V. Klinova, Anastasia E. Tsaregorodtseva, Artem V. Korotkov, Eugene A. Shuman, Larisa I. Privalova and Boris A. Katsnelson

Int. J. Mol. Sci. 2019, 20(7), 1778; https://doi.org/10.3390/ijms20071778 - 10 Apr 2019

Cited by 37 | Viewed by 4892

Abstract

Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m³ for 4 h a day 5 times a week for up to 10 months. The rat organism responded to this impact with changes in cytological and some biochemical [...] Read more.

Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m³ for 4 h a day 5 times a week for up to 10 months. The rat organism responded to this impact with changes in cytological and some biochemical characteristics of the bronchoalveolar lavage fluid along with a paradoxically little pronounced pulmonary pathology associated with a rather low chronic retention of nanoparticles in the lungs. There were various manifestations of systemic toxicity, including damage to the liver and kidneys; a likely allergic syndrome as indicated by some cytological signs; transient stimulation of erythropoiesis; and penetration of nickel into the brain from the nasal mucous membrane along the olfactory pathway. Against a picture of mild to moderate chronic toxicity of nickel, its in vivo genotoxic effect assessed by the degree of DNA fragmentation in nucleated blood cells (the RAPD test) was pronounced, tending to increasing with the length of the exposure period. When rats were given orally, in parallel with the toxic exposure, a set of innocuous substances with differing mechanisms of expected bioprotective action, the genotoxic effect of NiO-NPs was found to be substantially attenuated. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

12 pages, 2763 KiB

Open AccessArticle

Toxicological Evaluation of SiO₂ Nanoparticles by Zebrafish Embryo Toxicity Test

by Sandra Vranic, Yasuhito Shimada, Sahoko Ichihara, Masayuki Kimata, Wenting Wu, Toshio Tanaka, Sonja Boland, Lang Tran and Gaku Ichihara

Int. J. Mol. Sci. 2019, 20(4), 882; https://doi.org/10.3390/ijms20040882 - 18 Feb 2019

Cited by 59 | Viewed by 8407

Abstract

As the use of nanoparticles (NPs) is increasing, the potential toxicity and behavior of NPs in living systems need to be better understood. Our goal was to evaluate the developmental toxicity and bio-distribution of two different sizes of fluorescently-labeled SiO₂ NPs, 25 [...] Read more.

As the use of nanoparticles (NPs) is increasing, the potential toxicity and behavior of NPs in living systems need to be better understood. Our goal was to evaluate the developmental toxicity and bio-distribution of two different sizes of fluorescently-labeled SiO₂ NPs, 25 and 115 nm, with neutral surface charge or with different surface functionalization, rendering them positively or negatively charged, in order to predict the effect of NPs in humans. We performed a zebrafish embryo toxicity test (ZFET) by exposing the embryos to SiO₂ NPs starting from six hours post fertilization (hpf). Survival rate, hatching time, and gross morphological changes were assessed at 12, 24, 36, 48, 60, and 72 hpf. We evaluated the effect of NPs on angiogenesis by counting the number of sub-intestinal vessels between the second and seventh intersegmental vessels and gene expression analysis of vascular endothelial growth factor (VEGF) and VEGF receptors at 72 hpf. SiO₂ NPs did not show any adverse effects on survival rate, hatching time, gross morphology, or physiological angiogenesis. We found that SiO₂ NPs were trapped by the chorion up until to the hatching stage. After chemical removal of the chorion (dechorionation), positively surface-charged SiO₂ NPs (25 nm) significantly reduced the survival rate of the fish compared to the control group. These results indicate that zebrafish chorion acts as a physical barrier against SiO₂ NPs, and removing the chorions in ZFET might be necessary for evaluation of toxicity of NPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

17 pages, 3905 KiB

Open AccessArticle

Imaging of Metastatic Cancer Cells in Sentinel Lymph Nodes using Affibody Probes and Possibility of a Theranostic Approach

by Makoto Tsuchimochi, Haruka Yamaguchi, Kazuhide Hayama, Yasuo Okada, Tomoyuki Kawase, Takamasa Suzuki, Norio Tsubokawa, Noriaki Wada, Atsushi Ochiai, Satoshi Fujii and Hirofumi Fujii

Int. J. Mol. Sci. 2019, 20(2), 427; https://doi.org/10.3390/ijms20020427 - 19 Jan 2019

Cited by 9 | Viewed by 6105

Abstract

The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach [...] Read more.

The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach for developing a more efficient SLN biopsy procedure, we reported a two-stage imaging method combining lymphoscintigraphy and near-infrared (NIR) fluorescence imaging to depict metastatic cancer cells in SLNs in vivo. Furthermore, the theranostic potential of the combined procedure was examined by cell culture and xenograft mouse model. Anti-HER2 and anti-epidermal growth factor receptor (EGFR) affibody probes were used for NIR fluorescence imaging. Strong NIR fluorescence signal intensity of the anti-EGFR affibody probe was observed in SAS cells (EGFR positive). Radioactivity in the SLNs was clearly observed in the in vivo studies. High anti-EGFR affibody NIR fluorescence intensity was observed in the metastatic lymph nodes in mice. The addition of the IR700-conjugated anti-EGFR affibody to the culture medium decreased the proliferation of SAS cells. Decreased proliferation was shown in Ki-67 immunohistochemistry in xenograft tumors. Our data suggest that a two-stage combined imaging method using lymphoscintigraphy and affibody probes may offer the direct visualization of metastatic lymph nodes as an easily applied technique in SLN biopsy. Although further animal studies are required to assess the effect of treating lymphatic metastasis in this approach, our study results provide a foundation for the further development of this promising imaging and treatment strategy for earlier lymph node metastasis detection and treatment. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

15 pages, 3767 KiB

Open AccessArticle

Protein Food Matrix–ZnO Nanoparticle Interactions Affect Protein Conformation, but May not Be Biological Responses

by Song-Hwa Bae, Jin Yu, Tae Geol Lee and Soo-Jin Choi

Int. J. Mol. Sci. 2018, 19(12), 3926; https://doi.org/10.3390/ijms19123926 - 7 Dec 2018

Cited by 28 | Viewed by 4475

Abstract

Because of their nutritional value, zinc oxide (ZnO) nanoparticles (NPs) are applied as a dietary source of zinc, by direct addition to complex, multiple-component food matrices. The thereby occurring interactions of NPs with food matrices may have biological or toxic effects. In particular, [...] Read more.

Because of their nutritional value, zinc oxide (ZnO) nanoparticles (NPs) are applied as a dietary source of zinc, by direct addition to complex, multiple-component food matrices. The thereby occurring interactions of NPs with food matrices may have biological or toxic effects. In particular, NP interactions with food protein can lead to structural deformation of the latter, potentially changing its digestive efficiency and gastrointestinal absorption. In this study, interactions between ZnO NPs and a representative complex protein food matrix, skim milk, were compared with those between NPs and individual components of this food matrix (i.e., protein, saccharide, and mineral). The effects of the interactions on biological responses were investigated in terms of cytotoxicity, cellular uptake, intestinal transport, structural deformation for proteins, and digestive efficiency. The results demonstrated that the physicochemical properties of ZnO NPs were strongly influenced by the protein matrix type, leading to an increased dispersion stability in the complex protein matrix. However, these interactions did not affect cell proliferation, membrane damage, cellular uptake, intestinal transportation, or protein digestive efficiency, although a slight conformational change of proteins was observed in the presence of ZnO NPs. In conclusion, no toxic effects were observed, suggesting the safety of NPs when added to complex food matrices. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

13 pages, 3400 KiB

Open AccessArticle

Chitosan Hydrogel Beads Functionalized with Thymol-Loaded Solid Lipid–Polymer Hybrid Nanoparticles

by Taoran Wang and Yangchao Luo

Int. J. Mol. Sci. 2018, 19(10), 3112; https://doi.org/10.3390/ijms19103112 - 11 Oct 2018

Cited by 18 | Viewed by 8054

Abstract

In this study, the innovative and multifunctional nanoparticles–hydrogel nanocomposites made with chitosan hydrogel beads and solid lipid–polymer hybrid nanoparticles (SLPN) were prepared through conjugation between SLPN and chitosan beads. The SLPNs were first fabricated via coating the bovine serum albumin (BSA)-emulsified solid lipid [...] Read more.

In this study, the innovative and multifunctional nanoparticles–hydrogel nanocomposites made with chitosan hydrogel beads and solid lipid–polymer hybrid nanoparticles (SLPN) were prepared through conjugation between SLPN and chitosan beads. The SLPNs were first fabricated via coating the bovine serum albumin (BSA)-emulsified solid lipid nanoparticles with oxidized dextran. The aldehyde groups of the oxidized dextran on the surface of the SLPN enabled an in situ conjugation with the chitosan beads through the Schiff base linkage. The obtained nano-on-beads composite exhibited a spherical shape with a homogeneous size distribution. The successful conjugation of SLPN on the chitosan beads was confirmed by a Fourier transform infrared spectroscopy and a scanning electron microscope. The effects of the beads dosage (50, 100, 200, and 300 beads) and the incubation duration (30, 60, 90, 120, and 150 min) on the conjugation efficiency of SLPN onto the beads were comprehensively optimized. The optimal formulations were found to be a 200 bead dosage, with 30–90 min incubation duration groups. The optimal formulations were then used to encapsulate thymol, an antibacterial agent, which was studied as a model compound. After encapsulation, the thymol exhibited sustained release profiles in the phosphate buffer saline. The as-prepared nanoparticles–hydrogel nanocomposites reported in this proof-of-concept study hold promising features as a controlled-release antibacterial approach for improving food safety. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

13 pages, 2453 KiB

Open AccessArticle

Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

by Noriaki Nagai, Fumihiko Ogata, Miyu Ishii, Yuya Fukuoka, Hiroko Otake, Yosuke Nakazawa and Naohito Kawasaki

Int. J. Mol. Sci. 2018, 19(7), 2138; https://doi.org/10.3390/ijms19072138 - 23 Jul 2018

Cited by 32 | Viewed by 6507

Abstract

We previously designed a novel transdermal formulation containing ketoprofen solid nanoparticles (KET-NPs formulation), and showed that the skin penetration from the KET-NPs formulation was higher than that of a transdermal formulation containing ketoprofen microparticles (KET-MPs formulation). However, the precise mechanism for the skin [...] Read more.

We previously designed a novel transdermal formulation containing ketoprofen solid nanoparticles (KET-NPs formulation), and showed that the skin penetration from the KET-NPs formulation was higher than that of a transdermal formulation containing ketoprofen microparticles (KET-MPs formulation). However, the precise mechanism for the skin penetration from the KET-NPs formulation was not clear. In this study we investigated whether energy-dependent endocytosis relates to the transdermal delivery from a 1.5% KET-NPs formulation. Transdermal formulations were prepared by a bead mill method using additives including methylcellulose and carbopol 934. The mean particle size of the ketoprofen nanoparticles was 98.3 nm. Four inhibitors of endocytosis dissolved in 0.5% DMSO (54 μM nystatin, a caveolae-mediated endocytosis inhibitor; 40 μM dynasore, a clathrin-mediated endocytosis inhibitor; 2 μM rottlerin, a macropinocytosis inhibitor; 10 μM cytochalasin D, a phagocytosis inhibitor) were used in this study. In the transdermal penetration study using a Franz diffusion cell, skin penetration through rat skin treated with cytochalasin D was similar to the control (DMSO) group. In contrast to the results for cytochalasin D, skin penetration from the KET-NPs formulation was significantly decreased by treatment with nystatin, dynasore or rottlerin with penetrated ketoprofen concentration-time curves (AUC) values 65%, 69% and 73% of control, respectively. Furthermore, multi-treatment with all three inhibitors (nystatin, dynasore and rottlerin) strongly suppressed the skin penetration from the KET-NPs formulation with an AUC value 13.4% that of the control. In conclusion, we found that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis are all related to the skin penetration from the KET-NPs formulation. These findings provide significant information for the design of nanomedicines in transdermal formulations. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

19 pages, 3063 KiB

Open AccessArticle

Silver Nanoparticles: Two-Faced Neuronal Differentiation-Inducing Material in Neuroblastoma (SH-SY5Y) Cells

by Ahmed Abdal Dayem, Soo Bin Lee, Hye Yeon Choi and Ssang-Goo Cho

Int. J. Mol. Sci. 2018, 19(5), 1470; https://doi.org/10.3390/ijms19051470 - 15 May 2018

Cited by 16 | Viewed by 5854

Abstract

We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated [...] Read more.

We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated SH-SY5Y cells showed significantly higher reactive oxygen species (ROS) generation, stronger mitochondrial membrane depolarization, lower dual-specificity phosphatase expression, higher extracellular-signal-regulated kinase (ERK) phosphorylation, lower AKT phosphorylation, and lower expression of the genes encoding the antioxidant enzymes than RA-treated cells. Notably, pretreatment with N-acetyl-l-cysteine significantly abolished AgNP-induced neuronal differentiation, but not in that induced by RA. ERK inhibition, but not AKT inhibition, suppresses neurite growth that is induced by AgNP. Taken together, our results uncover the pivotal contribution of ROS in the AgNP-induced neuronal differentiation mechanism, which is different from that of RA. However, the negative consequence of AgNP-induced neurite growth may be high ROS generation and the downregulation of the expression of the genes encoding the antioxidant enzymes, which prompts the future consideration and an in-depth study of the application of AgNP-differentiated cells in neurodegenerative disease therapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

18 pages, 4739 KiB

Open AccessArticle

Effect of Amelogenin Coating of a Nano-Modified Titanium Surface on Bioactivity

by Chisato Terada, Satoshi Komasa, Tetsuji Kusumoto, Takayoshi Kawazoe and Joji Okazaki

Int. J. Mol. Sci. 2018, 19(5), 1274; https://doi.org/10.3390/ijms19051274 - 24 Apr 2018

Cited by 17 | Viewed by 6403

Abstract

The interactions between implants and host tissues depend on several factors. In particular, a growing body of evidence has demonstrated that the surface texture of an implant influences the response of the surrounding cells. The purpose of this study is to develop new [...] Read more.

The interactions between implants and host tissues depend on several factors. In particular, a growing body of evidence has demonstrated that the surface texture of an implant influences the response of the surrounding cells. The purpose of this study is to develop new implant materials aiming at the regeneration of periodontal tissues as well as hard tissues by coating nano-modified titanium with amelogenin, which is one of the main proteins contained in Emdogain^®. We confirmed by quartz crystal microbalance evaluation that amelogenin is easy to adsorb onto the nano-modified titanium surface as a coating. Scanning electron microscopy, scanning probe microscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy analyses confirmed that amelogenin coated the nano-modified titanium surface following alkali-treatment. In vitro evaluation using rat bone marrow and periodontal ligament cells revealed that the initial adhesion of both cell types and the induction of hard tissue differentiation such as cementum were improved by amelogenin coating. Additionally, the formation of new bone in implanted surrounding tissues was observed in in vivo evaluation using rat femurs. Together, these results suggest that this material may serve as a new implant material with the potential to play a major role in the advancement of clinical dentistry. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

13 pages, 38053 KiB

Open AccessArticle

In Vitro and In Vivo Osteogenic Activity of Titanium Implants Coated by Pulsed Laser Deposition with a Thin Film of Fluoridated Hydroxyapatite

by Luyuan Chen, Satoshi Komasa, Yoshiya Hashimoto, Shigeki Hontsu and Joji Okazaki

Int. J. Mol. Sci. 2018, 19(4), 1127; https://doi.org/10.3390/ijms19041127 - 10 Apr 2018

Cited by 32 | Viewed by 5126

Abstract

To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning electron microscopy (SEM) and scanning probe microscopy (SPM), while physicochemical properties were evaluated [...] Read more.

To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning electron microscopy (SEM) and scanning probe microscopy (SPM), while physicochemical properties were evaluated by attenuated reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Calcium deposition, osteocalcin production, and expression of osteoblast genes were significantly higher in rat bone marrow mesenchymal stem cells seeded on FHA-coated titanium than in cells seeded on uncoated titanium. Implantation into rat femurs also showed that the FHA-coated material had superior osteoinductive and osseointegration activity in comparison with that of traditional implants, as assessed by microcomputed tomography and histology. Thus, titanium coated with FHA holds promise as a dental implant material. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

13 pages, 8447 KiB

Open AccessArticle

HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells

by Haruka Yamaguchi, Kazuhide Hayama, Ichiro Sasagawa, Yasuo Okada, Tomoyuki Kawase, Norio Tsubokawa and Makoto Tsuchimochi

Int. J. Mol. Sci. 2018, 19(3), 908; https://doi.org/10.3390/ijms19030908 - 19 Mar 2018

Cited by 25 | Viewed by 6188

Abstract

We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage [...] Read more.

We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

28 pages, 5856 KiB

Open AccessArticle

Combined Subchronic Toxicity of Aluminum (III), Titanium (IV) and Silicon (IV) Oxide Nanoparticles and Its Alleviation with a Complex of Bioprotectors

by Ilzira A. Minigalieva, Boris A. Katsnelson, Larisa I. Privalova, Marina P. Sutunkova, Vladimir B. Gurvich, Vladimir Y. Shur, Ekaterina V. Shishkina, Irene E. Valamina, Oleg H. Makeyev, Vladimir G. Panov, Anatoly N. Varaksin, Tatiana V. Bushueva, Renata R. Sakhautdinova, Svetlana V. Klinova, Svetlana N. Solovyeva and Ekaterina Y. Meshtcheryakova

Int. J. Mol. Sci. 2018, 19(3), 837; https://doi.org/10.3390/ijms19030837 - 13 Mar 2018

Cited by 28 | Viewed by 4733

Abstract

Stable suspensions of metal/metalloid oxide nanoparticles (MeO-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in [...] Read more.

Stable suspensions of metal/metalloid oxide nanoparticles (MeO-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the MeO-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks before measuring a large number of functional, biochemical, morphological and cytological indices for the organism’s status. In many respects, the Al₂O₃-NP was found to be the most toxic species alone and the most dangerous component of the combinations studied. Mathematical modeling with the help of the Response Surface Methodology showed that, as well as in the case of any other binary toxic combinations previously investigated by us, the organism’s response to a simultaneous exposure to any two of the MeO-NP species under study was characterized by a complex interaction between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which outcome this type was estimated for and on effect and dose levels. With any third MeO-NP species acting in the background, the type of combined toxicity displayed by the other two remained virtually the same or changed significantly, becoming either more or less unfavorable. Various harmful effects produced by the (Al₂O₃-NP + TiO₂-NP + SiO₂-NP)-combination, including its genotoxicity, were substantially attenuated by giving the rats per os during the entire exposure period a complex of innocuous bioactive substances expected to increase the organism’s antitoxic resistance. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

11 pages, 3133 KiB

Open AccessArticle

“Nano-Ginseng” for Enhanced Cytotoxicity AGAINST Cancer Cells

by Lin Dai, Weiyan Zhu, Chuanling Si and Jiandu Lei

Int. J. Mol. Sci. 2018, 19(2), 627; https://doi.org/10.3390/ijms19020627 - 23 Feb 2018

Cited by 22 | Viewed by 5564

Abstract

Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol [...] Read more.

Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol nanoparticles (Rb1/PPD NPs), completely based on the protopanaxadiol-type extracts. The optimized nano-formulations demonstrated an appropriate size (~110 nm), high drug loading efficiency (~96.8%) and capacity (~27.9 wt %), long half-time in systemic circulation (nine-fold longer than free PPD), better antitumor effects in vitro and in vivo, higher accumulation at the tumor site and reduced damage to normal tissues. Importantly, this process of “nano-ginseng” production is a simple, scalable, green economy process. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

16 pages, 4467 KiB

Open AccessArticle

Effects of Interactions between ZnO Nanoparticles and Saccharides on Biological Responses

by Mi-Ran Go, Jin Yu, Song-Hwa Bae, Hyeon-Jin Kim and Soo-Jin Choi

Int. J. Mol. Sci. 2018, 19(2), 486; https://doi.org/10.3390/ijms19020486 - 6 Feb 2018

Cited by 35 | Viewed by 5081

Abstract

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food [...] Read more.

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food matrices, interactions between NPs and food components occur, which can affect biological systems. In this study, interactions between ZnO NPs and saccharides were investigated by measuring changes in hydrodynamic radius, zeta potential and solubility and by quantifying amounts of adsorbed saccharides on NPs; acacia honey, sugar mixtures (containing equivalent amounts of fructose, glucose, sucrose and maltose) and monosaccharide solutions were used as model compounds. Biological responses of NPs dispersed in different saccharides were also evaluated in human intestinal cells and rats in terms of cytotoxicity, cellular uptake, intestinal transport and oral absorption. The results demonstrate that the hydrodynamic radii and zeta potentials of NPs were highly affected by saccharides. In addition, trace nutrients influenced NP/saccharide interactions and interactive effects between saccharides on the interactions were found. NPs in all saccharides increased inhibition of cell proliferation and enhanced cellular uptake. Oral absorption of NPs was highly enhanced by 5% glucose, which is in-line with intestinal transport result. These findings show that ZnO NPs interact with saccharides and these interactions affects biological responses. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

19 pages, 7060 KiB

Open AccessArticle

Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

by Werner E. G. Müller, Meik Neufurth, Shunfeng Wang, Maximilian Ackermann, Rafael Muñoz-Espí, Qingling Feng, Qiang Lu, Heinz C. Schröder and Xiaohong Wang

Int. J. Mol. Sci. 2018, 19(2), 427; https://doi.org/10.3390/ijms19020427 - 31 Jan 2018

Cited by 23 | Viewed by 6465

Abstract

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form [...] Read more.

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts) and RUNX2 (chondrocyte differentiation). In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for treatment of bone metastases. The polyP particles are highlighted as genuine, smart, bioinspired nano/micro biomaterials. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

15878 KiB

Open AccessArticle

Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in Intravenously Exposed Mice

by Ping Xie, Sheng-Tao Yang, Tiantian He, Shengnan Yang and Xiao-Hai Tang

Int. J. Mol. Sci. 2017, 18(12), 2562; https://doi.org/10.3390/ijms18122562 - 29 Nov 2017

Cited by 45 | Viewed by 5559

Abstract

Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure [...] Read more.

Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure should be thoroughly investigated to ensure its safe use. Herein, we studied the bioaccumulation of CNSI in reticuloendothelial system (RES) organs and the corresponding toxicity to mice. After the intravenous injection of CNSI, no abnormal behavior of mice was observed during the 28-day observation period. The body weight increases were similar among the exposed groups and the control group. The parameters of hematology and serum biochemistry remained nearly unchanged, with very few of them showing significant changes. The low toxicity of CNSI was also reflected by the unchanged histopathological characteristics of these organs. The injection of CNSI did not induce higher apoptosis levels either. The slight oxidative stress was observed in RES organs at high dosages at day 7 post-exposure. The implication to the clinical applications and toxicological evaluations of carbon nanomaterials is discussed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

3387 KiB

Open AccessArticle

Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

by Einar Sulheim, Tore-Geir Iversen, Vu To Nakstad, Geir Klinkenberg, Håvard Sletta, Ruth Schmid, Anne Rein Hatletveit, Ane Marit Wågbø, Anders Sundan, Tore Skotland, Kirsten Sandvig and Ýrr Mørch

Int. J. Mol. Sci. 2017, 18(11), 2454; https://doi.org/10.3390/ijms18112454 - 18 Nov 2017

Cited by 44 | Viewed by 6548

Abstract

Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. [...] Read more.

Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100–200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

2800 KiB

Open AccessArticle

Targeted Delivery of siRNA with pH-Responsive Hybrid Gold Nanostars for Cancer Treatment

by Hongyan Zhu, Wanwan Liu, Ziting Cheng, Ke Yao, Yu Yang, Bohui Xu and Gaoxing Su

Int. J. Mol. Sci. 2017, 18(10), 2029; https://doi.org/10.3390/ijms18102029 - 22 Sep 2017

Cited by 30 | Viewed by 5731

Abstract

In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose [...] Read more.

In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling. Compared to GNS alone, 9R/DG-GNS (hydrazone) showed superior transfection efficiency. The expressions of cyclooxygenase-2 (COX-2) in HepG2 and SGC7901 cells were significantly suppressed by siRNA/9R/DG-GNS (hydrazone) complex. Notably, 9R/DG-GNS (hydrazone) possessed low cytotoxicity even at high concentrations in both normal cells and tumor cells. The combination treatment of siRNA/9R/DG-GNS (hydrazone) complex inhibited the cell growth rate by more than 75%. These results verified that the pH-responsive GNS complex is a promising siRNA delivery system for cancer therapy, and it is anticipated that near-infrared absorbing GNS with good photothermal conversion efficiency can be potentially used for photothermal therapy of tumors. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

3401 KiB

Open AccessCommunication

Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model

by Verena Damiani, Elisabetta Falvo, Giulio Fracasso, Luca Federici, Martina Pitea, Vincenzo De Laurenzi, Gianluca Sala and Pierpaolo Ceci

Int. J. Mol. Sci. 2017, 18(7), 1555; https://doi.org/10.3390/ijms18071555 - 18 Jul 2017

Cited by 35 | Viewed by 6146

Abstract

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is [...] Read more.

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS). This carrier displayed excellent therapeutic efficacy in a xenogenic pancreatic cancer model in vivo, leading to a significant increase in overall animal survival in treated mice. Herein, we describe the HFt-MP-PAS40-Dox efficacy against squamous cell carcinomas of the head and neck (HNSCC) with the goal of validating the application of our nano-drug for the treatment of different solid tumors. In addition, a tolerability study in healthy mice was also performed. The results indicate that HFt-MP-PAS40-Dox produced increased anti-tumor effects both in vitro and in vivo in comparison to the free drug in several HNSCC cell lines. In the acute toxicity studies, the maximum tolerated dose (MTD) of HFt-MP-PAS40-Dox was about 3.5 higher than the free drug: 25 mg/kg versus 7 mg/kg doxorubicin equivalents. Importantly, evaluation of heart tissues provided evidence that doxorubicin is less cardio-toxic when encapsulated inside the ferritin carrier. In conclusion, HFt-MP-PAS40-Dox may be administered safely at higher doses compared with the free drug, resulting in superior efficacy to control HNSCC malignancies. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

11384 KiB

Open AccessArticle

Effects of Titanium Mesh Surfaces-Coated with Hydroxyapatite/β-Tricalcium Phosphate Nanotubes on Acetabular Bone Defects in Rabbits

by Thuy-Duong Thi Nguyen, Tae-Sung Bae, Dae-hyeok Yang, Myung-sik Park and Sun-jung Yoon

Int. J. Mol. Sci. 2017, 18(7), 1462; https://doi.org/10.3390/ijms18071462 - 7 Jul 2017

Cited by 1 | Viewed by 6107

Abstract

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in [...] Read more.

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in vitro and in vivo. Nanotube-Ti mesh coated with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) was manufactured by an anodizing and a sintering method, respectively. An 8 mm diameter defect was created on each acetabulum of eight rabbits, then treated by grafting materials and covered by Ti meshes. At four and eight weeks, postoperatively, biopsies were performed for histomorphometric analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP-AT) meshes were superior with regard to the mineralized area at both four and eight weeks, as compared with that under untreated Ti meshes. Active bone regeneration at 2–4 weeks was stronger than at 6–8 weeks, particularly with treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes could enhance early contact bone formation on the mesh and, therefore, may reduce the collapse of Ti meshes into the defect, increasing the sufficiency of acetabular reconstruction. Finally, cyclic precalcification did not affect bone regeneration by biphasic grafting materials in vivo. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

9743 KiB

Open AccessArticle

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

by Zhaojun Li, Hui Huang, Lili Huang, Lianfang Du, Ying Sun and Yourong Duan

Int. J. Mol. Sci. 2017, 18(4), 815; https://doi.org/10.3390/ijms18040815 - 13 Apr 2017

Cited by 14 | Viewed by 5529

Abstract

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be [...] Read more.

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

7340 KiB

Open AccessArticle

Bioactivity of NANOZR Induced by Alkali Treatment

by Mariko Nishizaki, Satoshi Komasa, Yoichiro Taguchi, Hiroshi Nishizaki and Joji Okazaki

Int. J. Mol. Sci. 2017, 18(4), 780; https://doi.org/10.3390/ijms18040780 - 6 Apr 2017

Cited by 15 | Viewed by 4770 | Correction

Abstract

In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine [...] Read more.

In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine serum albumin adsorption rate, rat bone marrow (RBM) cell attachment, and capacity for inducing bone differentiation. NANOZR surfaces without and with alkali treatment served as the control and test groups, respectively. RBM cells were seeded in a microplate with the implant and cultured in osteogenic differentiation medium, and their differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, osteocalcin (OCN) production, calcium deposition, and osteogenic gene expression. The alkali-treated NANOZR surface increased ALP activity, OCN production, calcium deposition, and osteogenesis-related gene expression in attached RBM cells. These data suggest that alkali treatment enhances the osteogenesis-inducing capacity of NANOZR implants and may therefore improve their biointegration into alveolar bone. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

1988 KiB

Open AccessArticle

Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy

by Yu-Guo Yuan, Qiu-Ling Peng and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2017, 18(3), 569; https://doi.org/10.3390/ijms18030569 - 6 Mar 2017

Cited by 269 | Viewed by 12890

Abstract

Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance [...] Read more.

Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs) of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH) and lower adenosine triphosphate (ATP) levels compared to the control. Furthermore, AgNP-treated bacteria showed downregulated expression of glutathione (GSH), upregulation of glutathione S-transferase (GST), and downregulation of both superoxide dismutase (SOD) and catalase (CAT). These physiological and biochemical measurements were consistently observed in AgNP-treated bacteria, thereby suggesting that AgNPs can induce bacterial cell death. Thus, the above results represent conclusive findings on the mechanism of action of AgNPs against different types of bacteria. This study also demonstrates the promising use of nanoparticles as antibacterial agents for use in the biotechnology and biomedical industry. Furthermore, this study is the first to propose the mode of action of AgNPs against MDR pathogens isolated from goats infected with subclinical mastitis. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

4043 KiB

Open AccessArticle

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

by Marija Matulionyte, Dominyka Dapkute, Laima Budenaite, Greta Jarockyte and Ricardas Rotomskis

Int. J. Mol. Sci. 2017, 18(2), 378; https://doi.org/10.3390/ijms18020378 - 10 Feb 2017

Cited by 33 | Viewed by 7225

Abstract

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and [...] Read more.

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

2815 KiB

Open AccessArticle

Multifunctional Composite Microcapsules for Oral Delivery of Insulin

by Shaoping Sun, Na Liang, Xianfeng Gong, Weiwei An, Yoshiaki Kawashima, Fude Cui and Pengfei Yan

Int. J. Mol. Sci. 2017, 18(1), 54; https://doi.org/10.3390/ijms18010054 - 28 Dec 2016

Cited by 22 | Viewed by 6611

Abstract

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic [...] Read more.

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of −29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

2622 KiB

Open AccessArticle

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

by Yun-Jung Choi, Jung-Hyun Park, Jae Woong Han, Eunsu Kim, Oh Jae-Wook, Seung Yoon Lee, Jin-Hoi Kim and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2016, 17(12), 2077; https://doi.org/10.3390/ijms17122077 - 12 Dec 2016

Cited by 36 | Viewed by 6298

Abstract

The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used [...] Read more.

The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH⁺/CD133⁺ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH⁺/CD133⁺ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH⁺/CD133⁺ subpopulation of cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

5396 KiB

Open AccessArticle

Synthesis of Non-Toxic Silica Particles Stabilized by Molecular Complex Oleic-Acid/Sodium Oleate

by Catalin Ilie Spataru, Raluca Ianchis, Cristian Petcu, Cristina Lavinia Nistor, Violeta Purcar, Bogdan Trica, Sabina Georgiana Nitu, Raluca Somoghi, Elvira Alexandrescu, Florin Oancea and Dan Donescu

Int. J. Mol. Sci. 2016, 17(11), 1936; https://doi.org/10.3390/ijms17111936 - 19 Nov 2016

Cited by 10 | Viewed by 7368

Abstract

The present work is focused on the preparation of biocompatible silica particles from sodium silicate, stabilized by a vesicular system containing oleic acid (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the partial neutralization of oleic acid (OLA), with the [...] Read more.

The present work is focused on the preparation of biocompatible silica particles from sodium silicate, stabilized by a vesicular system containing oleic acid (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the partial neutralization of oleic acid (OLA), with the sodium cation present in the aqueous solutions of sodium silicate. At the molar ratio OLA/Na⁺ = 2:1, the molar ratio (OLA/OLANa = 1:1) required to form vesicles, in which the carboxyl and carboxylate groups have equal concentrations, was achieved. In order to obtain hydrophobically modified silica particles, octadecyltriethoxysilane (ODTES) was added in a sodium silicate sol–gel mixture at different molar ratios. The interactions between the octadecyl groups from the modified silica and the oleyl chains from the OLA/OLANa stabilizing system were investigated via simultaneous thermogravimetry (TG) and differential scanning calorimetry (DSC) (TG-DSC) analyses.A significant decrease in vaporization enthalpy and an increase in amount of ODTES were observed. Additionally, that the hydrophobic interaction between OLA and ODTES has a strong impact on the hybrids’ final morphology and on their textural characteristics was revealed. The highest hydrodynamic average diameter and the most negative ζ potential were recorded for the hybrid in which the ODTES/sodium silicate molar ratio was 1:5. The obtained mesoporous silica particles, stabilized by the OLA/OLANa vesicular system, may find application as carriers for hydrophobic bioactive molecules. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

5129 KiB

Open AccessArticle

A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway

by Hailong Zhang, Xiaogang Liu, Fengbo Wu, Feifei Qin, Ping Feng, Ting Xu, Xiang Li and Li Yang

Int. J. Mol. Sci. 2016, 17(5), 676; https://doi.org/10.3390/ijms17050676 - 17 May 2016

Cited by 26 | Viewed by 9096

Abstract

Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles [...] Read more.

Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles containing wogonin (WOG), which was named ACUPA-M-WOG. ACUPA-M-WOG was conventionally prepared using a self-assembling method, which produced stable particle size and ζ potential. Moreover, ACUPA-M-WOG showed good drug encapsulating capacity and drug release profiles. Fluorescence activated cell sorting (FACS) results suggested that ACUPA modified PEG-Cholesterol micelles could effectively enhance the drug uptake on PSMA(+) PCa cells, and the cytotoxicity of ACUPA-M-WOG was stronger than other controls according to in vitro cellular proliferation and apoptosis assays, separately through methyl thiazolyl tetrazolium (MTT) and Annexin V/Propidium Iodide (PI) staining. Finally, the molecular mechanisms of ACUPA-M-WOG’s effects on human PSMA(+) PCa were investigated, and were mainly the intrinsic or extrinsic apoptosis signaling pathways. The Western blot results suggested that ACUPA-M-WOG could enhance the WOG-induced apoptosis, which was mainly via the intrinsic signaling pathway rather than the extrinsic signaling pathway. In conclusion, ACUPA-M-WOG was successfully developed for WOG-selective delivery to PSMA(+) PCa cells and had stronger inhibition than free drugs, which might make it an effective strategy for PSMA(+) PCa. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

1015 KiB

Open AccessArticle

The Isolation of DNA by Polycharged Magnetic Particles: An Analysis of the Interaction by Zeta Potential and Particle Size

by Yazan Haddad, Kledi Xhaxhiu, Pavel Kopel, David Hynek, Ondrej Zitka and Vojtech Adam

Int. J. Mol. Sci. 2016, 17(4), 550; https://doi.org/10.3390/ijms17040550 - 20 Apr 2016

Cited by 22 | Viewed by 9894

Abstract

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 [...] Read more.

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 (phosphate-coated), and MAN164 (tripolyphosphate-coated). All particles were positive polycharged agglomerated monodispersed systems. Mean particle sizes were 0.48, 2.97, 2.93, and 3.67 μm for MAN37, MAN127, MAN164, and MAN158, respectively. DNA fragments exhibited negative zeta potential of −0.22 mV under binding conditions (high ionic strength, low pH, and dehydration). A decrease in zeta potential of particles upon exposure to DNA was observed with exception of MAN158 particles. The measured particle size of MAN164 particles increased by nearly twofold upon exposure to DNA. Quantitative PCR isolation of DNA with a high retrieval rate was observed by magnetic particles MAN127 and MAN164. Interaction between polycharged magnetic particles and DNA is mediated by various binding mechanisms such as hydrophobic and electrostatic interactions. Future development of DNA isolation technology requires an understanding of the physical and biochemical conditions of this process. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

2498 KiB

Open AccessArticle

A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery

by John C. Leach, Andrew Wang, Kaiming Ye and Sha Jin

Int. J. Mol. Sci. 2016, 17(3), 380; https://doi.org/10.3390/ijms17030380 - 14 Mar 2016

Cited by 52 | Viewed by 8584

Abstract

The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in [...] Read more.

The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox) was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA⁺ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

1844 KiB

Open AccessArticle

Evaluation of the Cytotoxic Behavior of Fungal Extracellular Synthesized Ag Nanoparticles Using Confocal Laser Scanning Microscope

by Taher A. Salaheldin, Sherif M. Husseiny, Abdullah M. Al-Enizi, Ahmed Elzatahry and Alan H. Cowley

Int. J. Mol. Sci. 2016, 17(3), 329; https://doi.org/10.3390/ijms17030329 - 3 Mar 2016

Cited by 21 | Viewed by 6822

Abstract

Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was [...] Read more.

Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was evident from the characteristic X-ray diffraction (XRD) pattern, high-resolution transmission electron Microscopy (HRTEM) and the particle size analyzer. The Ag nanoparticles were of dimension 40 ± 5 nm and spherical in shape. The study mainly focused on using the confocal laser scanning microscope (CLSM) to examine the cytotoxic activities of fungal synthesized Ag nanoparticles on a human breast carcinoma cell line MCF7 cell, which featured remarkable vacuolation, thus indicating a potent cytotoxic activity. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

11313 KiB

Open AccessArticle

Silica Nanoparticles Induce Oxidative Stress and Autophagy but Not Apoptosis in the MRC-5 Cell Line

by Sorina Nicoleta Petrache Voicu, Diana Dinu, Cornelia Sima, Anca Hermenean, Aurel Ardelean, Elena Codrici, Miruna Silvia Stan, Otilia Zărnescu and Anca Dinischiotu

Int. J. Mol. Sci. 2015, 16(12), 29398-29416; https://doi.org/10.3390/ijms161226171 - 10 Dec 2015

Cited by 95 | Viewed by 8634

Abstract

This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO₂ NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area [...] Read more.

This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO₂ NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area electron diffraction and X-ray diffraction. Our study showed a decreased cell viability and the induction of cellular oxidative stress as evidenced by an increased level of reactive oxygen species (ROS), carbonyl groups, and advanced oxidation protein products after 24, 48, and 72 h, as well as a decreased concentration of glutathione (GSH) and protein sulfhydryl groups. The protein expression of Hsp27, Hsp60, and Hsp90 decreased at all time intervals, while the level of protein Hsp70 remained unchanged during the exposure. Similarly, the expression of p53, MDM2 and Bcl-2 was significantly decreased for all time intervals, while the expression of Bax, a marker for apoptosis, was insignificantly downregulated. These results correlated with the increase of pro-caspase 3 expression. The role of autophagy in cellular response to SiO₂ NPs was demonstrated by a fluorescence-labeled method and by an increased level of LC3-II/LC3-I ratio. Taken together, our data suggested that SiO₂ NPs induced ROS-mediated autophagy in MRC-5 cells as a possible mechanism of cell survival. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

1828 KiB

Open AccessArticle

Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

by Noriaki Nagai, Chiaki Yoshioka, Yoshimasa Ito, Yoshinori Funakami, Hiroyuki Nishikawa and Atsufumi Kawabata

Int. J. Mol. Sci. 2015, 16(12), 29329-29344; https://doi.org/10.3390/ijms161226166 - 9 Dec 2015

Cited by 36 | Viewed by 7358

Abstract

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ± [...] Read more.

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZ_nano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZ_nano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZ_nano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZ_nano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZ_nano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

814 KiB

Open AccessArticle

Effects of Monotypic and Binary Mixtures of Metal Oxide Nanoparticles on Microbial Growth in Sandy Soil Collected from Artificial Recharge Sites

by Kyung-Seok Ko, Kyoochul Ha and In Chul Kong

Int. J. Mol. Sci. 2015, 16(11), 27967-27977; https://doi.org/10.3390/ijms161126066 - 24 Nov 2015

Cited by 7 | Viewed by 5695

Abstract

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) [...] Read more.

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) content, dehydrogenase activity (DHA), and viable cell counts (VCC). Microbial growth based on ATP content and VCC showed considerable differences depending on NP type and concentration, whereas DHA did not significantly change. In general, ZnO NPs showed the strongest effect on microbial growth in all measurements, showing an EC₅₀ value of 10.9 mg/L for ATP content. The ranking (EC₅₀) of NPs based on their effect on microbial growth assessed by ATP content and VCC was ZnO > Co₃O₄ > NiO > TiO₂. Upon exposure to binary NP mixtures, synergistic and additive modes of action were observed for ATP content and VCC, respectively. The ranges of observed (P(O)) and expected (P(E)) activity were 83%–92% and 78%–82% of the control (p-value 0.0010) based on ATP content and 78%–95% and 72%–94% of the control (p-value 0.8813) based on VCC under the tested conditions, respectively. The results indicate that the effects of NP mixtures on microbial growth in the sandy soil matrix were as great, or greater, than those of single NPs. Therefore, understanding the effects of single NPs and NP mixtures is essential for proper ecological risk assessment. Additionally, these findings demonstrate that the evaluation of NP effects may be profoundly influenced by the method of microbial growth measurement. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

2445 KiB

Open AccessArticle

Safety Profile of TiO₂-Based Photocatalytic Nanofabrics for Indoor Formaldehyde Degradation

by Guixin Cui, Yan Xin, Xin Jiang, Mengqi Dong, Junling Li, Peng Wang, Shumei Zhai, Yongchun Dong, Jianbo Jia and Bing Yan

Int. J. Mol. Sci. 2015, 16(11), 27721-27729; https://doi.org/10.3390/ijms161126055 - 19 Nov 2015

Cited by 14 | Viewed by 6678

Abstract

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded [...] Read more.

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded TNPs display very little release from nanofabrics (~0.0%) during a standard fastness to rubbing test. Assuming TNPs may fall off nanofabrics during their life cycles, we also examine the possible toxicity of TNPs to human cells. We found that up to a concentration of 220 μg/mL, they do not affect viability of human acute monocytic leukemia cell line THP-1 macrophages and human liver and kidney cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

2421 KiB

Open AccessArticle

Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles

by Myrtill Simkó, Sonja Tischler and Mats-Olof Mattsson

Int. J. Mol. Sci. 2015, 16(11), 26211-26236; https://doi.org/10.3390/ijms161125954 - 2 Nov 2015

Cited by 10 | Viewed by 6802

Abstract

The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness [...] Read more.

The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters’ size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

4290 KiB

Open AccessArticle

Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner

by Ewa Sawosz, Sławomir Jaworski, Marta Kutwin, Krishna Prasad Vadalasetty, Marta Grodzik, Mateusz Wierzbicki, Natalia Kurantowicz, Barbara Strojny, Anna Hotowy, Ludwika Lipińska, Joanna Jagiełło and André Chwalibog

Int. J. Mol. Sci. 2015, 16(10), 25214-25233; https://doi.org/10.3390/ijms161025214 - 23 Oct 2015

Cited by 36 | Viewed by 7692

Abstract

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the [...] Read more.

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

2118 KiB

Open AccessArticle

Staphylococcus aureus and MRSA Growth and Biofilm Formation after Treatment with Antibiotics and SeNPs

by Kristyna Cihalova, Dagmar Chudobova, Petr Michalek, Amitava Moulick, Roman Guran, Pavel Kopel, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2015, 16(10), 24656-24672; https://doi.org/10.3390/ijms161024656 - 16 Oct 2015

Cited by 71 | Viewed by 11174

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form biofilms in sensitive S. aureus and MRSA after the application of antibiotics (ATBs)—ampicillin, oxacillin and penicillin—and complexes of selenium nanoparticles (SeNPs) with these ATBs. The results suggest the strong inhibition effect of SeNPs in complexes with conventional ATBs. Using the impedance method, a higher disruption of biofilms was observed after the application of ATB complexes with SeNPs compared to the group exposed to ATBs without SeNPs. The biofilm formation was intensely inhibited (up to 99% ± 7% for S. aureus and up to 94% ± 4% for MRSA) after application of SeNPs in comparison with bacteria without antibacterial compounds whereas ATBs without SeNPs inhibited S. aureus up to 79% ± 5% and MRSA up to 16% ± 2% only. The obtained results provide a basis for the use of SeNPs as a tool for the treatment of bacterial infections, which can be complicated because of increasing resistance of bacteria to conventional ATB drugs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

2528 KiB

Open AccessArticle

Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies

by Naoko Ikuta, Takatsugu Endo, Shota Hosomi, Keita Setou, Shiori Tanaka, Noriko Ogawa, Hiromitsu Yamamoto, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Kenji Takahashi, Keiji Terao and Seiichi Matsugo

Int. J. Mol. Sci. 2015, 16(10), 24614-24628; https://doi.org/10.3390/ijms161024614 - 16 Oct 2015

Cited by 12 | Viewed by 7364

Abstract

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability [...] Read more.

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S–S and C–S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

3218 KiB

Open AccessArticle

Liver Toxicity of Cadmium Telluride Quantum Dots (CdTe QDs) Due to Oxidative Stress in Vitro and in Vivo

by Ting Zhang, Yuanyuan Hu, Meng Tang, Lu Kong, Jiali Ying, Tianshu Wu, Yuying Xue and Yuepu Pu

Int. J. Mol. Sci. 2015, 16(10), 23279-23299; https://doi.org/10.3390/ijms161023279 - 25 Sep 2015

Cited by 87 | Viewed by 8668

Abstract

With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of [...] Read more.

With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of cadmium telluride (CdTe) QDs in mice and murine hepatoma cells alpha mouse liver 12 (AML 12). CdTe QDs administration significantly increased the level of lipid peroxides marker malondialdehyde (MDA) in the livers of treated mice. Furthermore, CdTe QDs caused cytotoxicity in AML 12 cells in a dose- and time-dependent manner, which was likely mediated through the generation of reactive oxygen species (ROS) and the induction of apoptosis. An increase in ROS generation with a concomitant increase in the gene expression of the tumor suppressor gene p53, the pro-apoptotic gene Bcl-2 and a decrease in the anti-apoptosis gene Bax, suggested that a mitochondria mediated pathway was involved in CdTe QDs’ induced apoptosis. Finally, we showed that NF-E2-related factor 2 (Nrf2) deficiency blocked induced oxidative stress to protect cells from injury induced by CdTe QDs. These findings provide insights into the regulatory mechanisms involved in the activation of Nrf2 signaling that confers protection against CdTe QDs-induced apoptosis in hepatocytes. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Graphical abstract

3514 KiB

Open AccessArticle

Attenuation of Combined Nickel(II) Oxide and Manganese(II, III) Oxide Nanoparticles’ Adverse Effects with a Complex of Bioprotectors

by Ilzira A. Minigalieva, Boris A. Katsnelson, Larisa I. Privalova, Marina P. Sutunkova, Vladimir B. Gurvich, Vladimir Y. Shur, Ekaterina V. Shishkina, Irene E. Valamina, Oleg H. Makeyev, Vladimir G. Panov, Anatoly N. Varaksin, Ekaterina V. Grigoryeva and Ekaterina Y. Meshtcheryakova

Int. J. Mol. Sci. 2015, 16(9), 22555-22583; https://doi.org/10.3390/ijms160922555 - 17 Sep 2015

Cited by 51 | Viewed by 7486

Abstract

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected [...] Read more.

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected intraperitoneally (IP) to rats at a dose of 2.5 mg/kg 3 times a week up to 18 injections, either alone or in combination. A group of rats was injected with this combination with the background oral administration of a “bio-protective complex” (BPC) comprising pectin, vitamins A, C, E, glutamate, glycine, N-acetylcysteine, selenium, iodide and omega-3 PUFA, this composition having been chosen based on mechanistic considerations and previous experience. After the termination of injections, many functional and biochemical indices and histopathological features (with morphometric assessment) of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The Ni and Mn content of these organs was measured with the help of the atomic emission and electron paramagnetic resonance spectroscopies. We obtained blood leukocytes for performing the RAPD (Random Amplified Polymorphic DNA) test. Although both metallic NPs proved adversely bio-active in many respects considered in this study, Mn₃O₄-NPswere somewhat more noxious than NiO-NPs as concerns most of the non-specific toxicity manifestations and they induced more marked damage to neurons in the striatum and the hippocampus, which may be considered an experimental correlate of the manganese-induced Parkinsonism. The comparative solubility of the Mn₃O₄-NPs and NiO-NPs in a biological medium is discussed as one of the factors underlying the difference in their toxicokinetics and toxicities. The BPC has attenuated both the organ-systemic toxicity and the genotoxicity of Mn₃O₄-NPs in combination with NiO-NPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Bioactive Nanoparticles

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issues

Published Papers (150 papers)

Research