Special Issue "Metal-Based Drugs and Nanostructured Materials: New Trends in Bioactive Systems"

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

Deadline for manuscript submissions: closed (31 August 2020).

Special Issue Editor

Prof. Dr. Santiago Gómez-Ruiz
Website
Guest Editor
Department of Biology, Geology, Physics and Inorganic Chemistry, Universidad Rey Juan Carlos, Mostoles, Spain
Interests: nanomaterials; catalysis; photocatalysis; anticancer; metallodrugs
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Special Issue Information

Dear Colleagues,

Metal complexes are the basis of a wide variety of topics in Chemistry. For example, they are a current alternative for the treatment, diagnosis and marking of different diseases, constituting an interesting field of study in Medicinal Chemistry, Chemical Biology and Pharmaceutical Sciences.

However, metal complexes present a high number of drawbacks owing to their hydrophobic nature, low water solubility, limited stability and toxicity. Several strategies are now explored for the enhancement of the applicability of metal-based drugs in diagnosis and therapy.

In this context, nanostructured materials can protect metal-based drugs and help them to efficiently interact with biomolecules on surfaces and inside the cells, safely transporting drug molecules to target cells. In addition, nanostructures (lipid nanocapsules, polymeric nanoparticles, inorganic nanostructures, etc.) either encapsulating and protecting metallodrugs or as single nanosystems can ensure the proper and safe delivery of poorly water-soluble drugs or other agents.

In this context, this special issue will try to cover the most recent and cutting edge strategies on the support and encapsulation of metal complexes in nanosystems with therapeutic purposes.

The contributions of this Special Issue should be covering (but not limited to) the following topics:

  • The most recent synthetic methods for the preparation of novel metallodrugs and/or metallodrug-supported nanomaterials
  • Study of the therapeutic properties (in vitro or in vivo) of improved metal-based drugs and nanostructured materials functionalized with therapeutic metal complexes.
  • Analysis of the application of metal-based drugs or nanostructured materials in cell imaging or diagnosis
  • Study of the improvement of the bioavailability of metal-based drugs with the use of nanostructures as encapsulators.

Prof. Dr. Santiago Gómez-Ruiz
Guest Editor

Manuscript Submission Information

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Keywords

  • metal-based drugs
  • nanostructured materials
  • nanoparticles
  • nanomaterials
  • therapy
  • anticancer
  • diagnosis
  • imaging

Published Papers (6 papers)

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Research

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Open AccessArticle
Encapsulation of a Ru(II) Polypyridyl Complex into Polylactide Nanoparticles for Antimicrobial Photodynamic Therapy
Pharmaceutics 2020, 12(10), 961; https://doi.org/10.3390/pharmaceutics12100961 - 13 Oct 2020
Abstract
Antimicrobial photodynamic therapy (aPDT) also known as photodynamic inactivation (PDI) is a promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria. This therapy relies on the use of a molecule called photosensitizer capable of generating, from molecular oxygen, reactive oxygen [...] Read more.
Antimicrobial photodynamic therapy (aPDT) also known as photodynamic inactivation (PDI) is a promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria. This therapy relies on the use of a molecule called photosensitizer capable of generating, from molecular oxygen, reactive oxygen species including singlet oxygen under light irradiation to induce bacteria inactivation. Ru(II) polypyridyl complexes can be considered as potential photosensitizers for aPDT/PDI. However, to allow efficient treatment, they must be able to penetrate bacteria. This can be promoted by using nanoparticles. In this work, ruthenium-polylactide (RuPLA) nanoconjugates with different tacticities and molecular weights were prepared from a Ru(II) polypyridyl complex, RuOH. Narrowly-dispersed nanoparticles with high ruthenium loadings (up to 53%) and an intensity-average diameter < 300 nm were obtained by nanoprecipitation, as characterized by dynamic light scattering (DLS). Their phototoxicity effect was evaluated on four bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa) and compared to the parent compound RuOH. RuOH and the nanoparticles were found to be non-active towards Gram-negative bacterial strains. However, depending on the tacticity and molecular weight of the RuPLA nanoconjugates, differences in photobactericidal activity on Gram-positive bacterial strains have been evidenced whereas RuOH remained non active. Full article
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Open AccessArticle
A New Nano-Platform of Erythromycin Combined with Ag Nano-Particle ZnO Nano-Structure against Methicillin-Resistant Staphylococcus aureus
Pharmaceutics 2020, 12(9), 841; https://doi.org/10.3390/pharmaceutics12090841 - 02 Sep 2020
Abstract
Nano-particles have been combined with antibiotics in recent studies to overcome multidrug-resistant bacteria. Here, we synthesized a nano-material in which Ag nano-particles were assembled with a ZnO nano-structure to form an Ag-ZnO (AZO) nano-composite at low temperature. This material was combined with erythromycin [...] Read more.
Nano-particles have been combined with antibiotics in recent studies to overcome multidrug-resistant bacteria. Here, we synthesized a nano-material in which Ag nano-particles were assembled with a ZnO nano-structure to form an Ag-ZnO (AZO) nano-composite at low temperature. This material was combined with erythromycin (Ery), an antibiotic effective towards gram-positive bacteria, using three different approaches (AZO + Ery (AZE) [centrifuged (AZE1), used separately after 1-h gap (AZE2), without centrifugation (AZE3)]) to prepare a nano-antibiotic against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). X-ray diffraction analysis and transmission electron microscopy confirmed the presence of Ag nano-particles and ZnO nano-structure. The elemental and chemical state of the elements present in the AZO nano-composite were assessed by X-ray photoelectron spectroscopy. The antibacterial activity of AZE samples against both Escherichia coli and S. aureus strains including MRSA was evaluated in antibacterial and morphological analyses. The AZE3 sample showed greater antibacterial activity than the other samples and was comparable to erythromycin. AZE3 was ~20-fold less prone to developing bacterial resistance following multiple exposures to bacteria compared to erythromycin alone. The AZE3 nano-composite showed good biocompatibility with 293 human embryonic kidney cells. Our newly synthesized nano-platform antibiotics may be useful against multidrug-resistant gram-positive bacteria. Full article
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Open AccessArticle
Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines
Pharmaceutics 2020, 12(6), 512; https://doi.org/10.3390/pharmaceutics12060512 - 03 Jun 2020
Abstract
The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic [...] Read more.
The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors. Full article
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Open AccessArticle
The Synergism of Platinum-Gold Bimetallic Nanoconjugates Enhances 5-Fluorouracil Delivery In Vitro
Pharmaceutics 2019, 11(9), 439; https://doi.org/10.3390/pharmaceutics11090439 - 01 Sep 2019
Cited by 5
Abstract
Nanoparticle application has significantly impacted the field of medicine. The need to develop novel drugs with higher therapeutic potential has stimulated the development of innovative delivery strategies to mitigate the potent side effects associated with known chemotherapeutic drugs. This paper describes the synthesis [...] Read more.
Nanoparticle application has significantly impacted the field of medicine. The need to develop novel drugs with higher therapeutic potential has stimulated the development of innovative delivery strategies to mitigate the potent side effects associated with known chemotherapeutic drugs. This paper describes the synthesis of platinum-gold bimetallic nanoparticles (PtAuBNps), their functionalisation with chitosan, and entrapment of the anticancer drug 5-fluorouracil (5-FU). All PtAuBNps and their drug nanocomposites were physico-chemically characterised, displaying desirable properties with regards to shape, size (<120 nm) and colloidal stability. 5-FU binding and loading capacities in PtAuBNps were found to be 90.17% and 22.56%, respectively. In vitro cytotoxicity profiles determined using the MTT and SRB assays reflected up to 65% cell death in the MCF-7, HepG2 and Caco-2 cell lines. These nanocomposites exhibited excellent physiochemical attributes, high specificity towards cancer cells, with a pH-sensitive drug release in a simulated acidic tumour microenvironment through zero-order release kinetics. In addition, they possessed the potential to traverse the mucosal lining facilitating oral drug administration. Overall, 5-FU encapsulation improved the bioavailability of the drug in cancer cells, with the promise of enhancing its therapeutic effect, biocompatibility and safety. These positive results highlight PtAuBNps as promising in vitro delivery systems and merits future in vivo research. Full article
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Review

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Open AccessReview
Synthesis, Characterization, and Three-Dimensional Structure Generation of Zinc Oxide-Based Nanomedicine for Biomedical Applications
Pharmaceutics 2019, 11(11), 575; https://doi.org/10.3390/pharmaceutics11110575 - 04 Nov 2019
Cited by 11
Abstract
Zinc oxide (ZnO) nanoparticles have been studied as metal-based drugs that may be used for biomedical applications due to the fact of their biocompatibility. Their physicochemical properties, which depend on synthesis techniques involving physical, chemical, biological, and microfluidic reactor methods affect biological activity [...] Read more.
Zinc oxide (ZnO) nanoparticles have been studied as metal-based drugs that may be used for biomedical applications due to the fact of their biocompatibility. Their physicochemical properties, which depend on synthesis techniques involving physical, chemical, biological, and microfluidic reactor methods affect biological activity in vitro and in vivo. Advanced tool-based physicochemical characterization is required to identify the biological and toxicological effects of ZnO nanoparticles. These nanoparticles have variable morphologies and can be molded into three-dimensional structures to enhance their performance. Zinc oxide nanoparticles have shown therapeutic activity against cancer, diabetes, microbial infection, and inflammation. They have also shown the potential to aid in wound healing and can be used for imaging tools and sensors. In this review, we discuss the synthesis techniques, physicochemical characteristics, evaluation tools, techniques used to generate three-dimensional structures, and the various biomedical applications of ZnO nanoparticles. Full article
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Open AccessReview
Natural Diatom Biosilica as Microshuttles in Drug Delivery Systems
Pharmaceutics 2019, 11(10), 537; https://doi.org/10.3390/pharmaceutics11100537 - 15 Oct 2019
Cited by 10
Abstract
Unicellular diatom microalgae are a promising natural resource of porous biosilica. These microorganisms produce around their membrane a highly porous and extremely structured silica shell called frustule. Once harvested from living algae or from fossil sediments of diatomaceous earth, this biocompatible and non-toxic [...] Read more.
Unicellular diatom microalgae are a promising natural resource of porous biosilica. These microorganisms produce around their membrane a highly porous and extremely structured silica shell called frustule. Once harvested from living algae or from fossil sediments of diatomaceous earth, this biocompatible and non-toxic material offers an exceptional potential in the field of micro/nano-devices, drug delivery, theranostics, and other medical applications. The present review focused on the use of diatoms in the field of drug delivery systems, with the aim of presenting the different strategies implemented to improve the biophysical properties of this biosilica in terms of drug loading and release efficiency, targeted delivery, or site-specific binding capacity by surface functionalization. The development of composite materials involving diatoms for drug delivery applications is also described. Full article
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