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Biomedicines
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Gold and Silver Complexes in the Treatment of Diseases
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Gold and Silver Complexes in the Treatment of Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 26196

Special Issue Editor

Dr. María Jesús Rodríguez-Yoldi

E-Mail Website
Guest Editor
Department of Pharmacology and Physiology, Legal and Forensic Medicine, Physiology Unit, Faculty of Veterinary Medicine, University of Zaragoza, 50013 Zaragoza, Spain
Interests: intestinal absorption of nutrients; sepsis status (LPS, cytokines and inflammation); plant extracts and olive oil (squalene) for therapeutic purposes; encapsulation of plant extracts to improve their bioavailability; antioxidant and anti-inflammatory properties of plant extracts; antioxidant and anti-inflammatory markers; studies (modulators, pathways and targets) of apoptosis, necroptosis and autophagy; cell culture; cancer (mainly colon cancer) and diseases related to oxidative stress (cardiovascular, osteoarthritis and cancer); chemotherapeutics (gold complexes)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

At present, metal pharmaceuticals offer a new perspective in pharmacology and medicine. The growing development of so-called bioinorganic chemistry based on new drugs derived from metal complexes opens new possibilities in the treatment of diseases. The development of this new field began with the discovery of cisplatin as an effective antitumor. Other metal complexes such as gold and silver have been used since ancient times for their therapeutic properties. However, the rational use of gold in medicine began in the early 1920s with the discovery of the inhibitory properties of gold cyanine in the tuber bacillus. So far, various diseases have been treated with gold derivatives, including tuberculosis and rheumatoid arthritis. In recent decades, gold complexes have been tested against HIV for the treatment of AIDS, acute forms of chronic asthma, and pemphigus (an autoimmune skin disease) and in the treatment of malaria, Chagas disease, and cancer. On the other hand, silver complexes have been used in the treatment of childhood blindness (ophthalmia neonatorum) and as antimicrobial agents for many years, and their antitumor potential is currently being studied. In recent years, the use of metal complexes as chemotherapeutic agents is gaining importance. In this sense, the choice of the ligand is especially important since it can improve silver’s biological properties, such as the biodistribution, activity, and selectivity of the compound in relation to its lipophilic–hydrophilic balance, and in the case of silver, it can also affect its stability. Likewise, the use of nanoparticles as chemotherapeutic agents to transport metal complexes is beginning to be investigated.

This Special Issue may publish original research papers and reviews on aspects related to gold and silver complexes in the treatment of diseases, highlighting the mechanism of action and targets involved in its therapeutic properties.

Dr. María Jesús Rodríguez-Yoldi
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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gold complex
  • silver complex
  • ligands
  • health benefits
  • action mechanisms
  • targets

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Related Special Issue

Published Papers (7 papers)

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Research

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19 pages, 1798 KiB  
Article
Sulfonamide-Derived Dithiocarbamate Gold(I) Complexes Induce the Apoptosis of Colon Cancer Cells by the Activation of Caspase 3 and Redox Imbalance
by Javier Quero, José Carlos Royo, Beatrice Fodor, María Concepción Gimeno, Jesús Osada, María Jesús Rodríguez-Yoldi and Elena Cerrada
Biomedicines 2022, 10(6), 1437; https://doi.org/10.3390/biomedicines10061437 - 17 Jun 2022
Cited by 8 | Viewed by 2185
Abstract
Two new families of dithiocarbamate gold(I) complexes derived from benzenesulfonamide with phosphine or carbene as ancillary ligands have been synthesized and characterized. In the screening of their in vitro activity on human colon carcinoma cells (Caco-2), we found that the more lipophilic complexes—those [...] Read more.
Two new families of dithiocarbamate gold(I) complexes derived from benzenesulfonamide with phosphine or carbene as ancillary ligands have been synthesized and characterized. In the screening of their in vitro activity on human colon carcinoma cells (Caco-2), we found that the more lipophilic complexes—those with the phosphine PPh3—exhibited the highest anticancer activity whilst also displaying significant cancer cell selectivity. [Au(S2CNHSO2C6H5)(PPh3)] (1) and [Au(S2CNHSO2-p-Me-C6H4)(IMePropargyl)] (8) produce cell death, probably by intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation, causing cell cycle arrest in the G1 phase with p53 activation. Besides this, both complexes might act as multi-target anticancer drugs, as they inhibit the activity of the enzymes thioredoxin reductase (TrxR) and carbonic anhydrase (CA IX) with the alteration of the redox balance, and show a pro-oxidant effect. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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18 pages, 3274 KiB  
Article
Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells
by Javier Quero, Francesco Ruighi, Jesús Osada, M. Concepción Gimeno, Elena Cerrada and Maria Jesús Rodriguez-Yoldi
Biomedicines 2021, 9(12), 1848; https://doi.org/10.3390/biomedicines9121848 - 6 Dec 2021
Cited by 8 | Viewed by 2675
Abstract
Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules [...] Read more.
Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1,3,5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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18 pages, 1817 KiB  
Article
Selective Anticancer and Antimicrobial Metallodrugs Based on Gold(III) Dithiocarbamate Complexes
by Elisa Abás, Diego Aguirre-Ramírez, Mariano Laguna and Laura Grasa
Biomedicines 2021, 9(12), 1775; https://doi.org/10.3390/biomedicines9121775 - 26 Nov 2021
Cited by 13 | Viewed by 3129
Abstract
New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of [...] Read more.
New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of moderate strength to the BSA protein. Furthermore, none of the complexes exhibited reduction or decomposition reactions, presenting excellent physiological stability. The in vitro cytotoxic effect was evaluated on human colon cancer cell line Caco-2/TC7, and the complexes showed great antiproliferative activity and excellent selectivity, as much less effect was detected on normal Caco-2/TC7 cells. Most of the complexes exhibit antiproliferative activity that was better than or similar to auranofin, and at least nine times better than that of cisplatin. Its action mechanism is still under discussion since no evidence of cell cycle arrest was found, but an antioxidant role was shown for some of the selective complexes. All complexes were also tested as antimicrobial drugs, exhibiting good activity towards S. aureus and E. coli. bacteria and C. albicans and C. neoformans fungi. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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19 pages, 1607 KiB  
Article
Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
by Rossana Terracciano, Yareli Carcamo-Bahena, E. Brian Butler, Danilo Demarchi, Alessandro Grattoni and Carly S. Filgueira
Biomedicines 2021, 9(11), 1561; https://doi.org/10.3390/biomedicines9111561 - 28 Oct 2021
Cited by 7 | Viewed by 3319
Abstract
Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can [...] Read more.
Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using inductively coupled plasma—optical emission spectrometry (ICP-OES) and trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (** p < 0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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18 pages, 4731 KiB  
Article
Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
by Bilal Javed, Xinyi Zhao, Daxiang Cui, James Curtin and Furong Tian
Biomedicines 2021, 9(11), 1516; https://doi.org/10.3390/biomedicines9111516 - 21 Oct 2021
Cited by 28 | Viewed by 3564
Abstract
Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has [...] Read more.
Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the drug-loaded gold nanogels are spherical and exist in the size of 180 nm. The single and combinatorial toxicity effects of curcumin- and piperine-loaded Lignin-g-p (NIPAM-co-DMAEMA) gold nanogels were studied against U-251 MG GBM cells. A cytotoxicity analysis displayed anticancer properties. IC50 of curcumin- and piperine-loaded gold nanogels were recorded at 30 μM and 35 μM, respectively. Immunostaining and Western blot analysis confirmed the protein expression of caspase-3 and cleaved caspase-3 in cells treated with drug-loaded nanogels. Kinetic drug release revealed 86% release of hybrid curcumin–piperine from gold nanogel after 250 min at pH 4. Atomic absorption spectroscopic analysis confirmed that the drug-loaded nanogels have better internalization or association with the cancer cells than the GNPs or nano-gels alone. Morphological studies further confirmed that the curcumin and piperine nanogels penetrate the cells via endocytic pathways and induce caspase-3-related apoptosis. The experimental evidence shows the enhanced properties of combinatorial curcumin–piperine gold nanogels (IC50: 21 μM) to overcome the limitations of conventional chemotherapeutic treatments of glioma cells. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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Review

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23 pages, 2792 KiB  
Review
Biomedical Applications of Plant Extract-Synthesized Silver Nanoparticles
by Sohail Simon, Nicole Remaliah Samantha Sibuyi, Adewale Oluwaseun Fadaka, Samantha Meyer, Jamie Josephs, Martin Opiyo Onani, Mervin Meyer and Abram Madimabe Madiehe
Biomedicines 2022, 10(11), 2792; https://doi.org/10.3390/biomedicines10112792 - 2 Nov 2022
Cited by 54 | Viewed by 5626
Abstract
Silver nanoparticles (AgNPs) have attracted a lot of interest directed towards biomedical applications due in part to their outstanding anti-microbial activities. However, there have been many health-impacting concerns about their traditional synthesis methods, i.e., the chemical and physical methods. Chemical methods are commonly [...] Read more.
Silver nanoparticles (AgNPs) have attracted a lot of interest directed towards biomedical applications due in part to their outstanding anti-microbial activities. However, there have been many health-impacting concerns about their traditional synthesis methods, i.e., the chemical and physical methods. Chemical methods are commonly used and contribute to the overall toxicity of the AgNPs, while the main disadvantages of physical synthesis include high production costs and high energy consumption. The biological methods provide an economical and biocompatible option as they use microorganisms and natural products in the synthesis of AgNPs with exceptional biological properties. Plant extract-based synthesis has received a lot of attention and has been shown to resolve the limitations associated with chemical and physical methods. AgNPs synthesized using plant extracts provide a safe, cost-effective, and environment-friendly approach that produces biocompatible AgNPs with enhanced properties for use in a wide range of applications. The review focused on the use of plant-synthesized AgNPs in various biomedical applications as anti-microbial, anti-cancer, anti-inflammatory, and drug-delivery agents. The versatility and potential use of green AgNPs in the bio-medicinal sector provides an innovative alternative that can overcome the limitations of traditional systems. Thus proving green nanotechnology to be the future for medicine with continuous progress towards a healthier and safer environment by forming nanomaterials that are low- or non-toxic using a sustainable approach. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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26 pages, 14545 KiB  
Review
Current Developments of N-Heterocyclic Carbene Au(I)/Au(III) Complexes toward Cancer Treatment
by Alexia Tialiou, Jiamin Chin, Bernhard K. Keppler and Michael R. Reithofer
Biomedicines 2022, 10(6), 1417; https://doi.org/10.3390/biomedicines10061417 - 15 Jun 2022
Cited by 22 | Viewed by 4209
Abstract
Since their first discovery, N-heterocyclic carbenes have had a significant impact on organometallic chemistry. Due to their nature as strong σ-donor and π-acceptor ligands, they are exceptionally well suited to stabilize Au(I) and Au(III) complexes in biological environments. Over the last decade, [...] Read more.
Since their first discovery, N-heterocyclic carbenes have had a significant impact on organometallic chemistry. Due to their nature as strong σ-donor and π-acceptor ligands, they are exceptionally well suited to stabilize Au(I) and Au(III) complexes in biological environments. Over the last decade, the development of rationally designed NHCAu(I/III) complexes to specifically target DNA has led to a new “gold rush” in bioinorganic chemistry. This review aims to summarize the latest advances of NHCAu(I/III) complexes that are able to interact with DNA. Furthermore, the latest advancements on acyclic diamino carbene gold complexes with anticancer activity are presented as these typically overlooked NHC alternatives offer great additional design possibilities in the toolbox of carbene-stabilized gold complexes for targeted therapy. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases)
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