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Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (26 November 2018) | Viewed by 30309

Special Issue Editor

1. Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409, USA
2. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA
Interests: bioceramics; bone regeneratio; calcium phosphate; drug delivery matrices; biomimetic ceramics; tissue engineering; biological interactions of calcium phosphates; osteoinduction
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Special Issue Information

Dear Colleagues,

Manuscripts are invited for a Special Issue devoted to nanoparticles and nanostructured devices for targeted drug delivery, gene delivery, cancer therapy, and diagnostic imaging. Manuscripts describing original research and recent developments in topical areas such as synthesis, functionalization, mechanisms, and applications of these systems are of particular interest.

Prof. Mohamed Rahaman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • nanoparticles
  • nanomaterials
  • nanobiomaterials
  • drug delivery
  • gene delivery
  • cancer therapy
  • diagnostic imaging

Published Papers (6 papers)

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Research

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16 pages, 3153 KiB  
Article
Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair
by Shriya S. Srinivasan, Rajesh Seenivasan, Allison Condie, Stanton L. Gerson, Yanming Wang and Clemens Burda
Int. J. Mol. Sci. 2019, 20(3), 471; https://doi.org/10.3390/ijms20030471 - 22 Jan 2019
Cited by 3 | Viewed by 2857
Abstract
Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which [...] Read more.
Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies. Full article
(This article belongs to the Special Issue Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics)
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17 pages, 3277 KiB  
Article
Stearoyl-Chitosan Coated Nanoparticles Obtained by Microemulsion Cold Dilution Technique
by Daniela Chirio, Elena Peira, Simona Sapino, Chiara Dianzani, Alessandro Barge, Elisabetta Muntoni, Silvia Morel and Marina Gallarate
Int. J. Mol. Sci. 2018, 19(12), 3833; https://doi.org/10.3390/ijms19123833 - 30 Nov 2018
Cited by 27 | Viewed by 3713
Abstract
Chitosan is an excipient which has been studied thoroughly in research works thanks to its positive characteristics such as muco-adhesiveness and ability to open epithelial-tight-junctions. In this article, lipophilic stearoyl chitosan (ST-CS) was synthetized in order to anchor this polymer to lipid nanoparticles [...] Read more.
Chitosan is an excipient which has been studied thoroughly in research works thanks to its positive characteristics such as muco-adhesiveness and ability to open epithelial-tight-junctions. In this article, lipophilic stearoyl chitosan (ST-CS) was synthetized in order to anchor this polymer to lipid nanoparticles and prepare ST-CS-coated nanoparticles (ST-CS-NP) using the microemulsion cold dilution technique. Curcumin (CURC) was used as model drug. CURC-ST-CS-NP were characterized by dimensional analysis, zeta potential, drug entrapment, drug release; tested in vitro on Human Umbilical Vein Endothelial Cell (HUVEC) cells to study its cytotoxicity and on human pancreatic cancer cells (PANC-1) to determine inhibition ability; tested in rats to determine CURC blood profiles and biodistribution. CURC-ST-CS-NP had mean diameters in the range 200–400 nm and CURC entrapment up to 73%. These systems did not show cytotoxicity on HUVEC cells at all tested dilutions and revealed to be more effective than free CURC solution on PANC-1 cells at 5 and 10 µM CURC. Blood profile studies evidenced as CURC entrapment in NP prolonged the permanence of drug in the systemic circulation compared to CURC solution due to a certain stealth property of NP, probably attributable to hydrophilic chitosan coating. Biodistribution studies showed a smaller CURC concentration in RES organs when CURC-ST-CS-NP were administered. Full article
(This article belongs to the Special Issue Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics)
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29 pages, 7957 KiB  
Article
A Rapid Method for the Detection of Sarcosine Using SPIONs/Au/CS/SOX/NPs for Prostate Cancer Sensing
by Dagmar Uhlirova, Martina Stankova, Michaela Docekalova, Bozena Hosnedlova, Marta Kepinska, Branislav Ruttkay-Nedecky, Josef Ruzicka, Carlos Fernandez, Halina Milnerowicz and Rene Kizek
Int. J. Mol. Sci. 2018, 19(12), 3722; https://doi.org/10.3390/ijms19123722 - 22 Nov 2018
Cited by 25 | Viewed by 5002
Abstract
Background: Sarcosine is an amino acid that is formed by methylation of glycine and is present in trace amounts in the body. Increased sarcosine concentrations in blood plasma and urine are manifested in sarcosinemia and in some other diseases such as prostate cancer. [...] Read more.
Background: Sarcosine is an amino acid that is formed by methylation of glycine and is present in trace amounts in the body. Increased sarcosine concentrations in blood plasma and urine are manifested in sarcosinemia and in some other diseases such as prostate cancer. For this purpose, sarcosine detection using the nanomedicine approach was proposed. In this study, we have prepared superparamagnetic iron oxide nanoparticles (SPIONs) with different modified surface area. Nanoparticles (NPs) were modified by chitosan (CS), and sarcosine oxidase (SOX). SPIONs without any modification were taken as controls. Methods and Results: The obtained NPs were characterized by physicochemical methods. The size of the NPs determined by the dynamic light scattering method was as follows: SPIONs/Au/NPs (100–300 nm), SPIONs/Au/CS/NPs (300–700 nm), and SPIONs/Au/CS/SOX/NPs (600–1500 nm). The amount of CS deposited on the NP surface was found to be 48 mg/mL for SPIONs/Au/CS/NPs and 39 mg/mL for SPIONs/Au/CS/SOX/NPs, and repeatability varied around 10%. Pseudo-peroxidase activity of NPs was verified using sarcosine, horseradish peroxidase (HRP) and 3,3′,5,5′-tetramethylbenzidine (TMB) as a substrate. For TMB, all NPs tested evinced substantial pseudo-peroxidase activity at 650 nm. The concentration of SPIONs/Au/CS/SOX/NPs in the reaction mixture was optimized to 0–40 mg/mL. Trinder reaction for sarcosine detection was set up at 510 nm at an optimal reaction temperature of 37 °C and pH 8.0. The course of the reaction was linear for 150 min. The smallest amount of NPs that was able to detect sarcosine was 0.2 mg/well (200 µL of total volume) with the linear dependence y = 0.0011x − 0.0001 and the correlation coefficient r = 0.9992, relative standard deviation (RSD) 6.35%, limit of detection (LOD) 5 µM. The suggested method was further validated for artificial urine analysis (r = 0.99, RSD 21.35%, LOD 18 µM). The calculation between the detected and applied concentrations showed a high correlation coefficient (r = 0.99). NPs were tested for toxicity and no significant growth inhibition was observed in any model system (S. cerevisiae, S. aureus, E. coli). The hemolytic activity of the prepared NPs was similar to that of the phosphate buffered saline (PBS) control. The reaction system was further tested on real urine specimens. Conclusion: The proposed detection system allows the analysis of sarcosine at micromolar concentrations and to monitor changes in its levels as a potential prostate cancer marker. The whole system is suitable for low-cost miniaturization and point-of-care testing technology and diagnostic systems. This system is simple, inexpensive, and convenient for screening tests and telemedicine applications. Full article
(This article belongs to the Special Issue Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics)
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11 pages, 2072 KiB  
Article
PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells
by Rui Wang, Volkan Degirmenci, Hongchuan Xin, Ying Li, Liping Wang, Jiayu Chen, Xiaoyu Hu and Dianbao Zhang
Int. J. Mol. Sci. 2018, 19(8), 2230; https://doi.org/10.3390/ijms19082230 - 31 Jul 2018
Cited by 44 | Viewed by 4722
Abstract
Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (NPs) have been [...] Read more.
Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (NPs) have been developed and applied for siRNA delivery into GBM cells to silence repressor element 1-silencing transcription factor (REST). The prepared PEI-coated Fe3O4 NPs were characterized as magnetic nanoparticles with a positive charge, by transmission electronic microscopy, dynamic light-scattering analysis and a magnetometer. By gel retardation assay, the nanoparticles were found to form complexes with siRNA and the interaction proportion of NP to siRNA was 2.8:1. The cellular uptake of NP/siRNA complexes was verified by prussian blue staining, fluorescence labeling and flow cytometry in U-87 and U-251 GBM cells. Furthermore, the REST silencing examined by realtime polymerase chain reaction (PCR) and Western blotting presented significant reduction of REST in transcription and translation levels. Upon the treatment of NP/siRNA targeting REST, the GBM cell viabilities were inhibited and the migration capacities were repressed remarkably, analyzed by cell counting kit-8 and transwell assay separately. In this study, we demonstrated the PEI-coated Fe3O4 nanoparticle as a vehicle for therapeutic siRNA delivery, at an appropriate NP/siRNA weight ratio for REST silencing in GBM cells, inhibiting cell proliferation and migration efficiently. These might represent a novel potential treatment strategy for GBM. Full article
(This article belongs to the Special Issue Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics)
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Review

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20 pages, 5084 KiB  
Review
A Promising Biocompatible Platform: Lipid-Based and Bio-Inspired Smart Drug Delivery Systems for Cancer Therapy
by Min Woo Kim, Seung-Hae Kwon, Jung Hoon Choi and Aeju Lee
Int. J. Mol. Sci. 2018, 19(12), 3859; https://doi.org/10.3390/ijms19123859 - 04 Dec 2018
Cited by 44 | Viewed by 8831
Abstract
Designing new drug delivery systems (DDSs) for safer cancer therapy during pre-clinical and clinical applications still constitutes a considerable challenge, despite advances made in related fields. Lipid-based drug delivery systems (LBDDSs) have emerged as biocompatible candidates that overcome many biological obstacles. In particular, [...] Read more.
Designing new drug delivery systems (DDSs) for safer cancer therapy during pre-clinical and clinical applications still constitutes a considerable challenge, despite advances made in related fields. Lipid-based drug delivery systems (LBDDSs) have emerged as biocompatible candidates that overcome many biological obstacles. In particular, a combination of the merits of lipid carriers and functional polymers has maximized drug delivery efficiency. Functionalization of LBDDSs enables the accumulation of anti-cancer drugs at target destinations, which means they are more effective at controlled drug release in tumor microenvironments (TMEs). This review highlights the various types of ligands used to achieve tumor-specific delivery and discusses the strategies used to achieve the effective release of drugs in TMEs and not into healthy tissues. Moreover, innovative recent designs of LBDDSs are also described. These smart systems offer great potential for more advanced cancer therapies that address the challenges posed in this research area. Full article
(This article belongs to the Special Issue Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics)
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13 pages, 1569 KiB  
Review
Liposomes with an Ethanol Fraction as an Application for Drug Delivery
by Ewa Pilch and Witold Musiał
Int. J. Mol. Sci. 2018, 19(12), 3806; https://doi.org/10.3390/ijms19123806 - 29 Nov 2018
Cited by 34 | Viewed by 4644
Abstract
Liposomes containing a certain amount of ethanol are often referred to in the literature as ethosomes. Liposomes vary in size from 25 nm to 25,000 nm. Ethosomes are defined as lipids composed of phospholipids, ethanol, or isopropyl alcohol in quite high concentrations, and [...] Read more.
Liposomes containing a certain amount of ethanol are often referred to in the literature as ethosomes. Liposomes vary in size from 25 nm to 25,000 nm. Ethosomes are defined as lipids composed of phospholipids, ethanol, or isopropyl alcohol in quite high concentrations, and water. They enable active substances to reach the deep skin layers or even the general circulation. The structure of ethosomes allows for an increased penetration of the drug through two effects: the ethanolic effect and the ethosomal effect. Ethosomes can be obtained using three methods: the hot method, the cold method, and the classic method of mechanical dispersion. The literature describes many of the therapeutic groups of drugs that can be enclosed in ethosomal formulations. These include anti-viral drugs, antineoplastic drugs, antifungal drugs, hypnotic drugs, hormones, and many others. Ethosomes show important practical advantages compared to classic liposomes. It is necessary to conduct research with regard to real pharmaceutical systems using advanced physicochemical techniques. Full article
(This article belongs to the Special Issue Nanobiomaterials for Drug Delivery, Cancer Therapy and Diagnostics)
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