Affiliation:
1. Department of Chemistry and Chemical Biology Rutgers The State University of New Jersey 123 Bevier Road Piscataway NJ 08854 USA
Abstract
AbstractThe removal of dying cells, or efferocytosis, is an indispensable part of resolving inflammation. However, the inflammatory microenvironment of the atherosclerotic plaque frequently affects the biology of both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis‐resistant apoptotic cells expressing CD47 is developed. In both normal and inflammatory circumstances, CAR macrophages exhibit activity equivalent to antibody blockage. The surface of CAR macrophages is modified with reactive oxygen species (ROS)‐responsive therapeutic nanoparticles targeting the liver X receptor pathway to improve their cell effector activities. The combination of CAR and nanoparticle engineering activated lipid efflux pumps enhances cell debris clearance and reduces inflammation. It is further suggested that the undifferentiated CAR‐Ms can transmigrate within a mico‐fabricated vessel system. It is also shown that our CAR macrophage can act as a chimeric switch receptor (CSR) to withstand the immunosuppressive inflammatory environment. The developed platform has the potential to contribute to the advancement of next‐generation cardiovascular disease therapies and further studies include in vivo experiments.
Funder
National Science Foundation
New Jersey Commission on Spinal Cord Research
Alzheimer's Association
National Heart, Lung, and Blood Institute
National Institutes of Health
Cited by
6 articles.
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