Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
Baltazar Hiram Leal,
Brenda Velasco,
Adriana Cambón,
Alberto Pardo,
Javier Fernandez-Vega,
Lilia Arellano,
Abeer Al-Modlej,
Víctor X. Mosquera,
Alberto Bouzas,
Gerardo Prieto,
Silvia Barbosa,
Pablo Taboada
Affiliations
Baltazar Hiram Leal
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Brenda Velasco
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Adriana Cambón
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Alberto Pardo
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Javier Fernandez-Vega
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Lilia Arellano
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Abeer Al-Modlej
Department of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Víctor X. Mosquera
Cardiac Surgery Department, University Hospital of A Coruña, Biomedical Research Institute of A Coruña (INIBIC), 15006 A Coruña, Spain
Alberto Bouzas
Cardiac Surgery Department, University Hospital of A Coruña, Biomedical Research Institute of A Coruña (INIBIC), 15006 A Coruña, Spain
Gerardo Prieto
Institute of Materials, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Silvia Barbosa
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Pablo Taboada
Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
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.
