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Nanomaterials in Biological Systems: Opportunities and Challenges

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (20 January 2024) | Viewed by 33003

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Prof. Dr. Carolina Madeira Lucci

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Campus Universitário Darcy Ribeiro, Universidade de Brasília, Brasilia 70910-900, Brazil
Interests: biocompatibility; in vitro/in vivo cytotoxicity; in vivo interactions; hyperthermia

Prof. Dr. Ricardo Bentes Azevedo

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Guest Editor

Department of Genetics and Morphology, Universidade de Brasília, Brasilia 70910-900, Brazil
Interests: nanomedicine; photodynamic therapy; nanoemulsions; cancer treatments

Special Issue Information

Dear Colleagues,

Nanomaterials are a class of materials with unique properties that can be used in a wide range of applications and improve biomedical treatments. The different types of nanomaterials (inorganic and polymeric nanoparticles, liposomes, nanocrystals, nanotubes, dendrimers) can be specifically designed and functionalized to become biocompatible and to serve a specific a biomedical purpose. Numerous nanomaterials are being developed and studied for many applications, such as drug delivery, hyperthermia, imaging agents for diagnosis, and treatment of several conditions. Nanomaterials enable creating new therapeutic approaches and optimizing conventional treatments as they allow the delivery of drugs to the affected organ/tissue in a more specific and controlled way, as well as stimuli-responsive therapeutics. These features facilitate the use of lower doses and promote local rather than systemic action, avoiding or reducing side effects. Nanostructured materials also allow the development of treatments based on hyperthermia, such as thermocytolysis and thermoablation. Nonetheless, while nanomaterials present many potential advantages and open several opportunities for new biomedical and theragnostic applications, their interaction with biological systems still poses several challenges. Their short- and long-term effects on different cell types, organs, and body systems still need to be better understood.

The aim of this Special Issue is to explore the applications of nanostructured materials for biological and/or biomedical applications and the interactivity of these materials with different cells, organs, and biological systems.

Prof. Dr. Carolina Madeira Lucci
Prof. Dr. Ricardo Bentes Azevedo
Guest Editors

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Keywords

nanostructured materials
biomedical applications
biocompatibility
in vitro/in vivo cytotoxicity
in vivo interactions
pharmacokinetics
clearance in complex biological systems
theragnostic
nanomedicine

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Published Papers (10 papers)

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Research

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13 pages, 3608 KiB

Open AccessArticle

Up- and Down-Regulation of Enzyme Activity in Aggregates with Gold-Covered Magnetic Nanoparticles Triggered by Low-Frequency Magnetic Field

by Maxim M. Veselov, Maria V. Efremova, Andrey N. Prusov and Natalia L. Klyachko

Nanomaterials 2024, 14(5), 411; https://doi.org/10.3390/nano14050411 - 23 Feb 2024

Viewed by 1669

Abstract

The modern global trend toward sustainable processes that meet the requirements of “green chemistry” provides new opportunities for the broad application of highly active, selective, and specific enzymatic reactions. However, the effective application of enzymes in industrial processes requires the development of systems for the remote regulation of their activity triggered by external physical stimuli, one of which is a low-frequency magnetic field (LFMF). Magnetic nanoparticles (MNPs) transform the energy of an LFMF into mechanical forces and deformations applied to enzyme molecules on the surfaces of MNPs. Here, we demonstrate the up- and down-regulation of two biotechnologically important enzymes, yeast alcohol dehydrogenase (YADH) and soybean formate dehydrogenase (FDH), in aggregates with gold-covered magnetic nanoparticles (GCMNPs) triggered by an LFMF. Two types of aggregates, “dimeric” (with the enzyme attached to several GCMNPs simultaneously), with YADH or FDH, and “monomeric” (the enzyme attached to only one GCMNP), with FDH, were synthesized. Depending on the aggregate type (“dimeric” or “monomeric”), LFMF treatment led to a decrease (down-regulation) or an increase (up-regulation) in enzyme activity. For “dimeric” aggregates, we observed 67 ± 9% and 47 ± 7% decreases in enzyme activity under LFMF exposure for YADH and FDH, respectively. Moreover, in the case of YADH, varying the enzyme or the cross-linking agent concentration led to different magnitudes of the LFMF effect, which was more significant at lower enzyme and higher cross-linking agent concentrations. Different responses to LFMF exposure depending on cofactor presence were also demonstrated. This effect might result from a varying cofactor binding efficiency to enzymes. For the “monomeric” aggregates with FDH, the LFMF treatment caused a significant increase in enzyme activity; the magnitude of this effect depended on the cofactor type: we observed up to 40% enzyme up-regulation in the case of NADP⁺, while almost no effect was observed in the case of NAD⁺. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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13 pages, 3738 KiB

Open AccessArticle

Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes

by Lisa Zschiesche, Christina Janko, Bernhard Friedrich, Benjamin Frey, Julia Band, Stefan Lyer, Christoph Alexiou and Harald Unterweger

Nanomaterials 2023, 13(1), 14; https://doi.org/10.3390/nano13010014 - 20 Dec 2022

Cited by 9 | Viewed by 2238

Abstract

Dextran-coated superparamagnetic iron oxide nanoparticles (SPION^Dex) of various sizes can be used as contrast agents in magnetic resonance imaging (MRI) of different tissues, e.g., liver or atherosclerotic plaques, after intravenous injection. In previous studies, the blood compatibility and the absence of immunogenicity of SPION^Dex was demonstrated. The investigation of the interference of SPION^Dex with stimulated immune cell activation is the aim of this study. For this purpose, sterile and endotoxin-free SPION^Dex with different hydrodynamic sizes (30 and 80 nm) were investigated for their effect on monocytes, dendritic cells (DC) and lymphocytes in concentrations up to 200 µg/mL, which would be administered for use as an imaging agent. The cells were analyzed using flow cytometry and brightfield microscopy. We found that SPION^Dex were hardly taken up by THP-1 monocytes and did not reduce cell viability. In the presence of SPION^Dex, the phagocytosis of zymosan and E. coli by THP-1 was dose-dependently reduced. SPION^Dex neither induced the maturation of DCs nor interfered with their stimulated maturation. The particles did not induce lymphocyte proliferation or interfere with lymphocyte proliferation after stimulation. Since SPION^Dex rapidly distribute via the blood circulation in vivo, high concentrations were only reached locally at the injection site immediately after application and only for a very limited time. Thus, SPION^Dex can be considered immune compatible in doses required for use as an MRI contrast agent. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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18 pages, 4094 KiB

Open AccessArticle

Evaluation of Biocompatibility, Anti-Inflammatory, and Antinociceptive Activities of Pequi Oil-Based Nanoemulsions in In Vitro and In Vivo Models

by Andréia C. Pinheiro, Alicia S. Ombredane, Willie O. Pinheiro, Laise R. Andrade, Vitória R. P. Silva, Gisela J. Felice, Débora S. Alves, Aryanne F. Albernaz, Ariane P. Silveira, Milena C. F. Lima, Valdir F. Veiga-Junior, Thamis F. S. Gomes, Emanuel A. M. Damasceno, Fabiane H. Veiga-Souza, Paulo E. N. Souza, Sônia N. Báo, Eliza C. B. Duarte, Marcella L. B. Carneiro, Ricardo B. Azevedo, Mani I. Funez and Graziella A. Joanitti Show full author list Hide full author list

Nanomaterials 2022, 12(23), 4260; https://doi.org/10.3390/nano12234260 - 30 Nov 2022

Cited by 2 | Viewed by 2422

Abstract

Pequi oil (Caryocar brasiliense) contains bioactive compounds capable of modulating the inflammatory process; however, its hydrophobic characteristic limits its therapeutic use. The encapsulation of pequi oil in nanoemulsions can improve its biodistribution and promote its immunomodulatory effects. Thus, the objective of the present study was to formulate pequi oil-based nanoemulsions (PeNE) to evaluate their biocompatibility, anti-inflammatory, and antinociceptive effects in in vitro (macrophages—J774.16) and in vivo (Rattus novergicus) models. PeNE were biocompatible, showed no cytotoxic and genotoxic effects and no changes in body weight, biochemistry, or histology of treated animals at all concentrations tested (90–360 µg/mL for 24 h, in vitro; 100–400 mg/kg p.o. 15 days, in vivo). It was possible to observe antinociceptive effects in a dose-dependent manner in the animals treated with PeNE, with a reduction of 27 and 40% in the doses of 100 and 400 mg/kg of PeNE, respectively (p < 0.05); however, the treatment with PeNE did not induce edema reduction in animals with carrageenan-induced edema. Thus, the promising results of this study point to the use of free and nanostructured pequi oil as a possible future approach to a preventive/therapeutic complementary treatment alongside existing conventional therapies for analgesia. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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25 pages, 8466 KiB

Open AccessArticle

Development of New Natural Lipid-Based Nanoparticles Loaded with Aluminum-Phthalocyanine for Photodynamic Therapy against Melanoma

by Victor Carlos Mello, Victor Hugo Sousa Araújo, Karen Letycia Rodrigues de Paiva, Marina Mesquita Simões, Dafne Caroline Marques, Nelice Roberta da Silva Costa, Isadora Florêncio de Souza, Patricia Bento da Silva, Igor Santos, Raquel Almeida, Kelly Grace Magalhães, Sebastião William da Silva, Alexandre Silva Santos, Fabiane Veiga-Souza, Paulo Eduardo Narcizo Souza, Marina Arantes Raddichi, João Paulo Figueiró Longo, Jennifer Thayanne Cavalcante de Araújo, Luis Alexandre Muehlmann, Marlus Chorilli and Sônia Nair Báo Show full author list Hide full author list

Nanomaterials 2022, 12(20), 3547; https://doi.org/10.3390/nano12203547 - 11 Oct 2022

Cited by 17 | Viewed by 3223

Abstract

Photodynamic therapy (PDT) mediated by photosensitizers loaded in nanostructures as solid lipid nanoparticles has been pinpointed as an effective and safe treatment against different skin cancers. Amazon butters have an interesting lipid composition when it comes to forming solid lipid nanoparticles (SLN). In the present report, a new third-generation photosensitizing system consisting of aluminum-phthalocyanine associated with Amazon butter-based solid lipid nanoparticles (SLN-AlPc) is described. The SLN was developed using murumuru butter, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 40 nm was obtained. The study of the permeation of these AlPc did not permeate the analyzed skin, but when incorporated into the system, SLN-AlPc allowed permeation of almost 100% with 8 h of contact. It must be emphasized that SLN-AlPc was efficient for carrying aluminum-phthalocyanine photosensitizers and exhibited no toxicity in the dark. Photoactivated SLN-AlPc exhibited a 50% cytotoxicity concentration (IC₅₀) of 19.62 nM when applied to B16-F10 monolayers, and the type of death caused by the treatment was apoptosis. The exposed phospholipid phosphatidylserine was identified, and the treatment triggered a high expression of Caspase 3. A stable Amazon butter-based SLN-AlPc formulation was developed, which exhibits strong in vitro photodynamic activity on melanoma cells. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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19 pages, 4396 KiB

Open AccessArticle

In Vivo Evaluation of DMSA-Coated Magnetic Nanoparticle Toxicity and Biodistribution in Rats: A Long-Term Follow-Up

by Fernanda Paulini, Aline R. M. Marangon, Carolina L. Azevedo, Juliana L. M. Brito, Marcelle S. Lemos, Marcelo H. Sousa, Fabiane H. Veiga-Souza, Paulo E. N. Souza, Carolina M. Lucci and Ricardo B. Azevedo

Nanomaterials 2022, 12(19), 3513; https://doi.org/10.3390/nano12193513 - 8 Oct 2022

Cited by 4 | Viewed by 2082

Abstract

This work presents a long-term follow-up (300 days) of rats after a single intravenous injection of DMSA-coated magnetite nanoparticles (DMSA-MNP). The animals were systematically evaluated by hematological, biochemical, and ultrasound examinations, monitoring the same animal over time. In addition, oxidative stress evaluation, DMSA-MNP biodistribution, computerized tomography for ex vivo organs, and histopathology analysis were performed at the end of the experiment period. Overall, DMSA-MNP administration did not cause serious damage to the rats’ health over the course of 300 days post-administration. All animals presented hematological parameters within the normal limits, and no alterations on serum creatinine, urea, ALT, and AST were related to DMSA-MNP administration. Liver and spleen showed no important alterations in any of the examinations. The kidneys of treated animals displayed intermittent pelvis dilation at ultrasound analysis, but without damage to the organ parenchyma after 300 days. The lungs of treated animals presented a light interalveolar septal thickening, but the animals did not present any clinical respiratory symptom. Nanoparticles were not detected in the vital organs of treated animals 300 days after administration. This work represents the first assessment of the long-term effects of DMSA-MNP and goes a step further on the safety of its use for biomedical applications. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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15 pages, 3058 KiB

Open AccessArticle

Enhanced Uptake and Phototoxicity of C₆₀@albumin Hybrids by Folate Bioconjugation

by Andrea Cantelli, Marco Malferrari, Edoardo Jun Mattioli, Alessia Marconi, Giulia Mirra, Alice Soldà, Tainah Dorina Marforio, Francesco Zerbetto, Stefania Rapino, Matteo Di Giosia and Matteo Calvaresi

Nanomaterials 2022, 12(19), 3501; https://doi.org/10.3390/nano12193501 - 6 Oct 2022

Cited by 11 | Viewed by 2778

Abstract

Fullerenes are considered excellent photosensitizers, being highly suitable for photodynamic therapy (PDT). A lack of water solubility and low biocompatibility are, in many instances, still hampering the full exploitation of their potential in nanomedicine. Here, we used human serum albumin (HSA) to disperse fullerenes by binding up to five fullerene cages inside the hydrophobic cavities. Albumin was bioconjugated with folic acid to specifically address the folate receptors that are usually overexpressed in several solid tumors. Concurrently, tetramethylrhodamine isothiocyanate, TRITC, a tag for imaging, was conjugated to C₆₀@HSA in order to build an effective phototheranostic platform. The in vitro experiments demonstrated that: (i) HSA disperses C₆₀ molecules in a physiological environment, (ii) HSA, upon C₆₀ binding, maintains its biological identity and biocompatibility, (iii) the C₆₀@HSA complex shows a significant visible-light-induced production of reactive oxygen species, and (iv) folate bioconjugation improves both the internalization and the PDT-induced phototoxicity of the C₆₀@HSA complex in HeLa cells. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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8 pages, 1597 KiB

Open AccessArticle

Safety of Lavender Oil-Loaded Niosomes for In Vitro Culture and Biomedical Applications

by Janice de M. V. Vilela, Saeid Moghassemi, Arezoo Dadashzadeh, Marie-Madeleine Dolmans, Ricardo B. Azevedo and Christiani A. Amorim

Nanomaterials 2022, 12(12), 1999; https://doi.org/10.3390/nano12121999 - 10 Jun 2022

Cited by 14 | Viewed by 2874

Abstract

(1) Background: Essential oils have long been used as therapeutic agents. Lavender (Lavandula angustifolia) oil (LO) is an antispasmodic, anticonvulsant, relaxant, painkilling, and antimicrobial essential oil investigated as a natural substance for biomedical therapies. Nanoparticles have shown significant promise in improving drug delivery and efficacy. Considering these benefits, the aim of this study was to evaluate the toxicity of LO and lavender oil niosomes (LONs) in stem cells and myofibroblast models cultured in vitro. (2) Methods: Adipose tissue-derived stem cells and myometrial cells were cultured with LO or LONs at different concentrations (0, 0.016%, 0.031%, and 0.063%) and toxicity was evaluated with PrestoBlue™ and live/dead assay using calcein and ethidium homodimer. (3) Results: Cell viability was similar to controls in all groups, except in 0.063% LO for myometrial cells, which showed lower viability than the control medium. (4) Conclusion: These results suggest that both LO and LONs are safe for cell culture and may be used for pharmaceutical and biomedical therapies in future applications in regenerative medicine. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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16 pages, 3883 KiB

Open AccessArticle

Fish Oil Nanoemulsion Supplementation Attenuates Bleomycin-Induced Pulmonary Fibrosis BALB/c Mice

by Danielle Galdino de Souza, Débora Silva Santos, Karina Smidt Simon, José Athayde Vasconcelos Morais, Luísa Coutinho Coelho, Thyago José Arruda Pacheco, Ricardo Bentes Azevedo, Anamélia Lorenzetti Bocca, César Augusto Melo-Silva and João Paulo Figueiró Longo

Nanomaterials 2022, 12(10), 1683; https://doi.org/10.3390/nano12101683 - 14 May 2022

Cited by 20 | Viewed by 3606

Abstract

Diets rich in omega-3 or -6 fatty acids will produce different profiles for cell membranes phospholipid constitutions. Omegas 3 and 6 are part of the diet and can modulate the inflammatory profile. We evaluated the effects of the oral absorption of fish oil, when associated with a lipid nanoemulsion in an experimental pulmonary inflammatory model. Pulmonary fibrosis is a disease associated with excessive extracellular matrix deposition. We determined to investigate the morphophysiological mechanisms in mice that were pretreated after induction with bleomycin (BLM). The pretreatment was for 21 days with saline solution, sunflower oil (SO), fish oil (FO), and fish oil nanoemulsion (NEW3). The animals received a daily dose of 50 mg/Kg of docosahexaenoic acid DHA and 10 mg/Kg eicosapentaenoic (EPA) (100 mg/Kg), represented by a daily dose of 40 µL of NEW3. The blank group was treated with the same amount daily (40 µL) during the 21 days of pretreatment. The animals were treated with SO and FO, 100 mg/Kg (containing 58 mg/Kg of polyunsaturated fats/higher% linoleic acid) and 100 mg/Kg (50 mg/Kg of DHA and 10 mg/Kg EPA), respectively. A single dose of 5 mg/mL (50 μL) bleomycin sulfate, by the intratracheal surgical method in BALB/cAnNTac (BALB/c). NEW3 significantly reduced fibrotic progression, which can be evidenced by the protection from loss of body mass, increase in respiratory incursions per minute, decreased spacing of alveolar septa, decreased severity of fibrosis, and changes in the respiratory system. NEW3 attenuated the inflammatory changes developed in the experimental model of pulmonary fibrosis, while group SO showed a significant increase in inflammatory changes. This concluded that the presented results demonstrated that is possible to positively modulate the immune and inflamamtory response to an external agressor, by changing the nutitional intake of specific fatty acids, such as omega-3 placed in fish oil. Moreover, these benefits can be improved by the nanoencapsulation of fish oil in lipid nanoemulsions. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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19 pages, 2270 KiB

Open AccessEditor’s ChoiceReview

Current Challenges in Image-Guided Magnetic Hyperthermia Therapy for Liver Cancer

by Anirudh Sharma, Erik Cressman, Anilchandra Attaluri, Dara L. Kraitchman and Robert Ivkov

Nanomaterials 2022, 12(16), 2768; https://doi.org/10.3390/nano12162768 - 12 Aug 2022

Cited by 12 | Viewed by 3876

Abstract

For patients diagnosed with advanced and unresectable hepatocellular carcinoma (HCC), liver transplantation remains the best option to extend life. Challenges with organ supply often preclude liver transplantation, making palliative non-surgical options the default front-line treatments for many patients. Even with imaging guidance, success following treatment remains inconsistent and below expectations, so new approaches are needed. Imaging-guided thermal therapy interventions have emerged as attractive procedures that offer individualized tumor targeting with the potential for the selective targeting of tumor nodules without impairing liver function. Furthermore, imaging-guided thermal therapy with added standard-of-care chemotherapies targeted to the liver tumor can directly reduce the overall dose and limit toxicities commonly seen with systemic administration. Effectiveness of non-ablative thermal therapy (hyperthermia) depends on the achieved thermal dose, defined as time-at-temperature, and leads to molecular dysfunction, cellular disruption, and eventual tissue destruction with vascular collapse. Hyperthermia therapy requires controlled heat transfer to the target either by in situ generation of the energy or its on-target conversion from an external radiative source. Magnetic hyperthermia (MHT) is a nanotechnology-based thermal therapy that exploits energy dissipation (heat) from the forced magnetic hysteresis of a magnetic colloid. MHT with magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs) requires the targeted deposition of MNPs into the tumor, followed by exposure of the region to an AMF. Emerging modalities such as magnetic particle imaging (MPI) offer additional prospects to develop fully integrated (theranostic) systems that are capable of providing diagnostic imaging, treatment planning, therapy execution, and post-treatment follow-up on a single platform. In this review, we focus on recent advances in image-guided MHT applications specific to liver cancer Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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27 pages, 1959 KiB

Open AccessReview

Recent Advances in Antimicrobial Nano-Drug Delivery Systems

by Tong-Xin Zong, Ariane Pandolfo Silveira, José Athayde Vasconcelos Morais, Marina Carvalho Sampaio, Luis Alexandre Muehlmann, Juan Zhang, Cheng-Shi Jiang and Shan-Kui Liu

Nanomaterials 2022, 12(11), 1855; https://doi.org/10.3390/nano12111855 - 29 May 2022

Cited by 55 | Viewed by 6926

Abstract

Infectious diseases are among the major health issues of the 21st century. The substantial use of antibiotics over the years has contributed to the dissemination of multidrug resistant bacteria. According to a recent report by the World Health Organization, antibacterial (ATB) drug resistance has been one of the biggest challenges, as well as the development of effective long-term ATBs. Since pathogens quickly adapt and evolve through several strategies, regular ATBs usually may result in temporary or noneffective treatments. Therefore, the demand for new therapies methods, such as nano-drug delivery systems (NDDS), has aroused huge interest due to its potentialities to improve the drug bioavailability and targeting efficiency, including liposomes, nanoemulsions, solid lipid nanoparticles, polymeric nanoparticles, metal nanoparticles, and others. Given the relevance of this subject, this review aims to summarize the progress of recent research in antibacterial therapeutic drugs supported by nanobiotechnological tools. Full article

(This article belongs to the Special Issue Nanomaterials in Biological Systems: Opportunities and Challenges)

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