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Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (25 December 2021) | Viewed by 32595

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Special Issue Editors

Prof. Dr. Alessandro F. Martins

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Guest Editor

Laboratory of Materials, Macromolecules, and Composites (LaMMAC), Federal University of Technology - Paraná (UTFPR), 86812-460 Apucarana, PR, Brazil
Interests: drug delivery; electrospinning; layer-by-layer; scaffolds; wound dressings; antimicrobial coatings; hydrogels; polysaccharides; cytocompatibility; hemocompatibility; polymer-based composites; metallic nanoparticles; mammalian cells
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Prof. Dr. Matt Kipper

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Co-Guest Editor

Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO, USA
Interests: polysaccharides; tissue engineering; blood–material interactions; orthopedic applications; protein–surface interactions; nanomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gold nanoparticles (AuNPs) are cytocompatible and have enormous potential for biomedical application. We highlight cancer treatments using photothermal and imaging therapies and cancer diagnosis due to localized surface plasmon resonance properties. Because of their high surface area to volume ratios, AuNPs often present instability in body fluids. Proteins and ionic species interact with AuNPs, promoting aggregation. To overcome this disadvantage, AuNP-based polymer composites are created, following ex-situ and in-situ strategies. Polymers stabilize AuNPs due to hindrance and repulsion forces supported by ionized sites on polymer-capping agents. Polymers can also coordinate with AuNPs, protecting them against aggregation. Biopolymers improve biomedical AuNP response, providing durability and enhanced cytocompatibility. Polymer-stabilized AuNP composites are used as drug delivery devices, sensors, scaffolds, wound dressings, coatings, and materials for nonconventional cancer therapies.

This Special Issue invites researchers to submit papers concerning AuNPs and AuNP/polymer composites applied as drug delivery platforms, photothermal and imaging agents, biosensors, wound dressings, scaffolds, and antimicrobial coatings, highlighting the progress in the current biomedicine landscape.

Prof. Dr. Alessandro F. Martins
Prof. Dr. Matt Kipper
Guest Editor

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Keywords

drug delivery
anisotropic gold nanoparticles
scaffolds
wound dressings
wound healing
biopolymers
cancer therapies
functionalization, antimicrobial coatings

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Published Papers (10 papers)

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Research

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15 pages, 2330 KiB

Open AccessArticle

Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

by Alexander Zaboronok, Sergey Taskaev, Olga Volkova, Ludmila Mechetina, Anna Kasatova, Tatiana Sycheva, Kei Nakai, Dmitrii Kasatov, Aleksandr Makarov, Iaroslav Kolesnikov, Ivan Shchudlo, Timofey Bykov, Evgeniia Sokolova, Alexey Koshkarev, Vladimir Kanygin, Aleksandr Kichigin, Bryan J. Mathis, Eiichi Ishikawa and Akira Matsumura

Pharmaceutics 2021, 13(9), 1490; https://doi.org/10.3390/pharmaceutics13091490 - 16 Sep 2021

Cited by 12 | Viewed by 3471

Abstract

Boron neutron capture therapy (BNCT) is an anticancer modality realized through ¹⁰B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 10⁸ cm⁻²s⁻¹. Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k—depth-related irradiation coefficient, N—number of activated gold atoms, n—boron concentration (ppm), and m—the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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17 pages, 3282 KiB

Open AccessArticle

Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

by Courtney van Ballegooie, Alice Man, Alessia Pallaoro, Marcel Bally, Byron D. Gates and Donald T. Yapp

Pharmaceutics 2021, 13(9), 1407; https://doi.org/10.3390/pharmaceutics13091407 - 4 Sep 2021

Cited by 3 | Viewed by 2585

Abstract

Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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12 pages, 28720 KiB

Open AccessArticle

The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System

by Adewale O. Oladipo, Thabang C. Lebepe, Vuyelwa Ncapayi, Ncediwe Tsolekile, Sundararajan Parani, Sandile P. Songca, Shiro Mori, Tetsuya Kodama and Oluwatobi S. Oluwafemi

Pharmaceutics 2021, 13(9), 1359; https://doi.org/10.3390/pharmaceutics13091359 - 28 Aug 2021

Cited by 8 | Viewed by 2933

Abstract

Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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13 pages, 4155 KiB

Open AccessArticle

Collagenase Activity of Bromelain Immobilized at Gold Nanoparticle Interfaces for Therapeutic Applications

by Adrianne M. M. Brito, Vitor Oliveira, Marcelo Y. Icimoto and Iseli L. Nantes-Cardoso

Pharmaceutics 2021, 13(8), 1143; https://doi.org/10.3390/pharmaceutics13081143 - 27 Jul 2021

Cited by 14 | Viewed by 3276

Abstract

Bromelain (Bro) is a multiprotein complex extracted from the pineapple plant Ananas comosus, composed of at least eight cysteine proteases. Bro has a wide range of applications in medicine and industry, where the stability of its active proteases is always a major concern. The present study describes the improvement of stability and gain of specific activity in the enzymatic content of Bro immobilized on gold nanoparticles (GNPs). GNPs were synthesized in situ using Bro as the reducing and stabilizing agents and characterized by surface plasmon resonance and transmission electron microscopy. Consistent with the structural changes observed by circular dichroism analysis, the association with GNPs affected enzyme activity. The active Bro immobilized on GNPs (NanoBro) remained stable under storage and gained thermal stability consistent with a thermophilic enzyme. Proteolytic assays were performed on type I collagen membranes using fluorescence spectroscopy of O-phthaldialdehyde (OPA), changes in the membrane superficial structure, and topography by scanning electron microscopy, FTIR, and scanning laser confocal microscopy. Another characteristic of the NanoBro observed was the significant increase in susceptibility to the inhibitory effect of E-64, indicating a gain in cysteine protease activity. The higher stability and specific activity of NanoBro contributed to the broadening and improvement of Bro applications. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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18 pages, 11664 KiB

Open AccessArticle

Phosphatidylserine-Gold Nanoparticles (PS-AuNP) Induce Prostate and Breast Cancer Cell Apoptosis

by Allan Radaic, Nam E. Joo, Soo-Hwan Jeong, Seong-II Yoo, Nicholas Kotov and Yvonne L. Kapila

Pharmaceutics 2021, 13(7), 1094; https://doi.org/10.3390/pharmaceutics13071094 - 17 Jul 2021

Cited by 11 | Viewed by 4498

Abstract

Prostate and breast cancer are the current leading causes of new cancer cases in males and females, respectively. Phosphatidylserine (PS) is an essential lipid that mediates macrophage efferocytosis and is dysregulated in tumors. Therefore, developing therapies that selectively restore PS may be a potential therapeutic approach for carcinogenesis. Among the nanomedicine strategies for delivering PS, biocompatible gold nanoparticles (AuNPs) have an extensive track record in biomedical applications. In this study, we synthesized biomimetic phosphatidylserine-caped gold nanoparticles (PS-AuNPs) and tested their anticancer potential in breast and prostate cancer cells in vitro. We found that both cell lines exhibited changes in cell morphology indicative of apoptosis. After evaluating for histone-associated DNA fragments, a hallmark of apoptosis, we found significant increases in DNA fragmentation upon PS-AuNP treatment compared to the control treatment. These findings demonstrate the use of phosphatidylserine coupled with gold nanoparticles as a potential treatment for prostate and breast cancer. To the best of our knowledge, this is the first time that a phosphatidylserine-capped AuNP has been examined for its therapeutic potential in cancer therapy. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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19 pages, 2287 KiB

Open AccessArticle

Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status

by Helen Yarimet Lorenzo-Anota, Diana G. Zarate-Triviño, Jorge Alberto Uribe-Echeverría, Andrea Ávila-Ávila, José Raúl Rangel-López, Ana Carolina Martínez-Torres and Cristina Rodríguez-Padilla

Pharmaceutics 2021, 13(7), 942; https://doi.org/10.3390/pharmaceutics13070942 - 24 Jun 2021

Cited by 8 | Viewed by 2675

Abstract

(1) Background: Chitosan-coated gold nanoparticles (CH-AuNPs) have important theranostic applications in biomedical sciences, including cancer research. However, although cell cytotoxicity has been studied in cancerous cells, little is known about their effect in proliferating primary leukocytes. Here, we assessed the effect of CH-AuNPs and the implication of ROS on non-cancerous endothelial and fibroblast cell lines and in proliferative lymphoid cells. (2) Methods: The Turkevich method was used to synthetize gold nanoparticles. We tested cell viability, cell death, ROS production, and cell cycle in primary lymphoid cells, compared with non-cancer and cancer cell lines. Concanavalin A (ConA) or lipopolysaccharide (LPS) were used to induce proliferation on lymphoid cells. (3) Results: CH-AuNPs presented high cytotoxicity and ROS production against cancer cells compared to non-cancer cells; they also induced a different pattern of ROS production in peripheral blood mononuclear cells (PBMCs). No significant cell-death difference was found in PBMCs, splenic mononuclear cells, and bone marrow cells (BMC) with or without a proliferative stimuli. (4) Conclusions: Taken together, our results highlight the selectivity of CH-AuNPs to cancer cells, discarding a consistent cytotoxicity upon proliferative cells including endothelial, fibroblast, and lymphoid cells, and suggest their application in cancer treatment without affecting immune cells. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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19 pages, 5780 KiB

Open AccessArticle

Biopolymer Composites with Ti/Au Nanostructures and Their Antibacterial Properties

by Petr Slepička, Dominik Fajstavr, Markéta Krejčová, Silvie Rimpelová, Nikola Slepičková Kasálková, Zdeňka Kolská and Václav Švorčík

Pharmaceutics 2021, 13(6), 826; https://doi.org/10.3390/pharmaceutics13060826 - 2 Jun 2021

Cited by 4 | Viewed by 2676

Abstract

In this study, we have aimed at the preparation and characterization of poly-l-lactic acid (PLLA) composites with antibacterial properties. Thin bilayers of titanium and gold of various thickness ratios were deposited on PLLA by a cathode sputtering method; selected samples were subsequently thermally treated. The surface morphology of the prepared composites was studied by atomic force, scanning electron, and laser confocal microscopy. The chemical properties of the composites were determined by X-ray photoelectron and energy-dispersive X-ray spectroscopy in combination with contact angle and zeta potential analyses. The antibacterial properties of selected samples were examined against a Gram-negative bacterial strain of E. coli. We have found that a certain combination of Au and Ti nanolayers in combination with heat treatment leads to the formation of a unique wrinkled pattern. Moreover, we have developed a simple technique by which a large-scale sample modification can be easily produced. The dimensions of wrinkles can be tailored by the sequence and thickness of the deposited metals. A selected combination of gold, titanium, and heat treatment led to the formation of a nanowrinkled pattern with excellent antibacterial properties. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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27 pages, 3430 KiB

Open AccessArticle

Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains

by Sylwia Joanna Chmielewska, Karol Skłodowski, Joanna Depciuch, Piotr Deptuła, Ewelina Piktel, Krzysztof Fiedoruk, Patrycja Kot, Paulina Paprocka, Kamila Fortunka, Tomasz Wollny, Przemysław Wolak, Magdalena Parlinska-Wojtan, Paul B. Savage and Robert Bucki

Pharmaceutics 2021, 13(3), 425; https://doi.org/10.3390/pharmaceutics13030425 - 22 Mar 2021

Cited by 27 | Viewed by 4287 | Correction

Abstract

Background: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. Methods: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLS_b) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. Results: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. Conclusions: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH₃ from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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Review

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29 pages, 3880 KiB

Open AccessReview

Gold-Polymer Nanocomposites for Future Therapeutic and Tissue Engineering Applications

by Panangattukara Prabhakaran Praveen Kumar and Dong-Kwon Lim

Pharmaceutics 2022, 14(1), 70; https://doi.org/10.3390/pharmaceutics14010070 - 28 Dec 2021

Cited by 33 | Viewed by 4213

Abstract

Gold nanoparticles (AuNPs) have been extensively investigated for their use in various biomedical applications. Owing to their biocompatibility, simple surface modifications, and electrical and unique optical properties, AuNPs are considered promising nanomaterials for use in in vitro disease diagnosis, in vivo imaging, drug delivery, and tissue engineering applications. The functionality of AuNPs may be further expanded by producing hybrid nanocomposites with polymers that provide additional functions, responsiveness, and improved biocompatibility. Polymers may deliver large quantities of drugs or genes in therapeutic applications. A polymer alters the surface charges of AuNPs to improve or modulate cellular uptake efficiency and their biodistribution in the body. Furthermore, designing the functionality of nanocomposites to respond to an endo- or exogenous stimulus, such as pH, enzymes, or light, may facilitate the development of novel therapeutic applications. In this review, we focus on the recent progress in the use of AuNPs and Au-polymer nanocomposites in therapeutic applications such as drug or gene delivery, photothermal therapy, and tissue engineering. Full article

(This article belongs to the Special Issue Application of Gold Nanoparticles and Gold-Based Polymer Composites in Biomedicine)

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