RT Journal Article
T1 Combined therapeutics for atherosclerosis treatment using polymeric nanovectors
A1 Hiram Leal, Baltazar
A1 Velasco Rodríguez, Brenda
A1 Cambón Freire, Adriana
A1 Pardo Montero, Alberto
A1 Fernández Vega, Javier
A1 Arellano, Lilia G.
A1 Al-Modlej, Abeer
A1 Mosquera, Víctor X.
A1 Bouzas, Alberto
A1 Prieto Estévez, Gerardo
K1 Nanoparticles
K1 Combination therapy
K1 Atherosclerosis
K1 miRNA
K1 Statin
K1 Inflammation
AB 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.
PB MDPI
YR 2022
FD 2022-01-22
LK https://hdl.handle.net/10347/43958
UL https://hdl.handle.net/10347/43958
LA eng
NO Leal, B.H.; Velasco, B.; Cambón, A.; Pardo, A.; Fernandez-Vega, J.; Arellano, L.; Al-Modlej, A.; Mosquera, V.X.; Bouzas, A.; Prieto, G.; et al. Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors. Pharmaceutics 2022, 14, 258. https://doi.org/10.3390/pharmaceutics14020258
DS Minerva
RD 29 abr 2026