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Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors

Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve syne...

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Autores principales: Leal, Baltazar Hiram, Velasco, Brenda, Cambón, Adriana, Pardo, Alberto, Fernandez-Vega, Javier, Arellano, Lilia, Al-Modlej, Abeer, Mosquera, Víctor X., Bouzas, Alberto, Prieto, Gerardo, Barbosa, Silvia, Taboada, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879452/
https://www.ncbi.nlm.nih.gov/pubmed/35213991
http://dx.doi.org/10.3390/pharmaceutics14020258
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author Leal, Baltazar Hiram
Velasco, Brenda
Cambón, Adriana
Pardo, Alberto
Fernandez-Vega, Javier
Arellano, Lilia
Al-Modlej, Abeer
Mosquera, Víctor X.
Bouzas, Alberto
Prieto, Gerardo
Barbosa, Silvia
Taboada, Pablo
author_facet Leal, Baltazar Hiram
Velasco, Brenda
Cambón, Adriana
Pardo, Alberto
Fernandez-Vega, Javier
Arellano, Lilia
Al-Modlej, Abeer
Mosquera, Víctor X.
Bouzas, Alberto
Prieto, Gerardo
Barbosa, Silvia
Taboada, Pablo
author_sort Leal, Baltazar Hiram
collection PubMed
description Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.
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spelling pubmed-88794522022-02-26 Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors Leal, Baltazar Hiram Velasco, Brenda Cambón, Adriana Pardo, Alberto Fernandez-Vega, Javier Arellano, Lilia Al-Modlej, Abeer Mosquera, Víctor X. Bouzas, Alberto Prieto, Gerardo Barbosa, Silvia Taboada, Pablo Pharmaceutics Article Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines. MDPI 2022-01-22 /pmc/articles/PMC8879452/ /pubmed/35213991 http://dx.doi.org/10.3390/pharmaceutics14020258 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leal, Baltazar Hiram
Velasco, Brenda
Cambón, Adriana
Pardo, Alberto
Fernandez-Vega, Javier
Arellano, Lilia
Al-Modlej, Abeer
Mosquera, Víctor X.
Bouzas, Alberto
Prieto, Gerardo
Barbosa, Silvia
Taboada, Pablo
Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
title Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
title_full Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
title_fullStr Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
title_full_unstemmed Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
title_short Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
title_sort combined therapeutics for atherosclerosis treatment using polymeric nanovectors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879452/
https://www.ncbi.nlm.nih.gov/pubmed/35213991
http://dx.doi.org/10.3390/pharmaceutics14020258
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