The study aims to enhance the efferocytosis of apoptotic cells (ACs) by developing a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis-resistant ACs expressing CD47. The CAR macrophages are modified with reactive oxygen species (ROS)-responsive therapeutic nanoparticles targeting the liver X receptor (LXR) pathway to improve their cell effector activities. The combination of CAR and nanoparticle engineering activates lipid efflux pumps, enhancing cell debris clearance and reducing inflammation. The undifferentiated CAR-Ms can transmigrate within a micro-fabricated vessel system and act as a chimeric switch receptor (CSR) to withstand the immunosuppressive inflammatory environment. The developed platform has potential applications in next-generation cardiovascular disease therapies, with in vivo experiments planned for further validation.The study aims to enhance the efferocytosis of apoptotic cells (ACs) by developing a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis-resistant ACs expressing CD47. The CAR macrophages are modified with reactive oxygen species (ROS)-responsive therapeutic nanoparticles targeting the liver X receptor (LXR) pathway to improve their cell effector activities. The combination of CAR and nanoparticle engineering activates lipid efflux pumps, enhancing cell debris clearance and reducing inflammation. The undifferentiated CAR-Ms can transmigrate within a micro-fabricated vessel system and act as a chimeric switch receptor (CSR) to withstand the immunosuppressive inflammatory environment. The developed platform has potential applications in next-generation cardiovascular disease therapies, with in vivo experiments planned for further validation.