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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/2/258 |
| _version_ | 1797477222461734912 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Baltazar Hiram Leal |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T21:14:35Z |
| format | Article |
| id | doaj.art-0643b73da223443597ab62d694642759 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:14:35Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0643b73da223443597ab62d6946427592023-11-23T21:36:16ZengMDPI AGPharmaceutics1999-49232022-01-0114225810.3390/pharmaceutics14020258Combined Therapeutics for Atherosclerosis Treatment Using Polymeric NanovectorsBaltazar Hiram Leal0Brenda Velasco1Adriana Cambón2Alberto Pardo3Javier Fernandez-Vega4Lilia Arellano5Abeer Al-Modlej6Víctor X. Mosquera7Alberto Bouzas8Gerardo Prieto9Silvia Barbosa10Pablo Taboada11Colloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainDepartment of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaCardiac Surgery Department, University Hospital of A Coruña, Biomedical Research Institute of A Coruña (INIBIC), 15006 A Coruña, SpainCardiac Surgery Department, University Hospital of A Coruña, Biomedical Research Institute of A Coruña (INIBIC), 15006 A Coruña, SpainInstitute of Materials, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainColloids and Polymers Physics Group, Department of Particle Physics, Faculty of Physics and Health Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainAtherosclerosis 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.https://www.mdpi.com/1999-4923/14/2/258nanoparticlescombination therapyatherosclerosismiRNAstatininflammation |
| spellingShingle | 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 Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors Pharmaceutics nanoparticles combination therapy atherosclerosis miRNA statin inflammation |
| 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 | nanoparticles combination therapy atherosclerosis miRNA statin inflammation |
| url | https://www.mdpi.com/1999-4923/14/2/258 |
| work_keys_str_mv | AT baltazarhiramleal combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT brendavelasco combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT adrianacambon combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT albertopardo combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT javierfernandezvega combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT liliaarellano combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT abeeralmodlej combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT victorxmosquera combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT albertobouzas combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT gerardoprieto combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT silviabarbosa combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors AT pablotaboada combinedtherapeuticsforatherosclerosistreatmentusingpolymericnanovectors |