传出细胞增多
材料科学
巨噬细胞
纳米技术
纳米颗粒
表面改性
脂质信号
吞噬作用
肝X受体
细胞生物学
生物化学
生物
化学工程
受体
工程类
体外
基因
转录因子
核受体
作者
Skylar T Chuang,Joshua B. Stein,Sarah Nevins,Cemile Kilic Bekta,H. Cho,Wan‐Kyu Ko,Hyun‐Jun Jang,Jihun Ha,Ki‐Bum Lee
标识
DOI:10.1002/adma.202308377
摘要
Abstract The 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, we developed a chimeric antigen receptor (CAR) macrophage that could target and engulf phagocytosis‐resistant apoptotic cells expressing CD47. In both normal and inflammatory circumstances, CAR macrophages exhibited activity equivalent to antibody blockage. The surface of CAR macrophages was 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, enhanced cell debris clearance, and reduced inflammation. We further suggest that the undifferentiated CAR‐Ms can transmigrate within a mico‐fabricated vessel system. We also show our CAR macrophage can act as a Chimeric Switch Receptor (CSR) to withstand the immunosuppressive inflammatory environments through enhanced stimulation via CD47‐SIRPα interaction. Based on our current understanding, our developed platform has the potential to contribute to the advancement of next‐generation cardiovascular disease therapies, but further studies, especially in vivo experiments, might be needed to assess its efficacy and safety fully. This article is protected by copyright. All rights reserved
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