逻辑门控递药系统用于肿瘤免疫治疗前沿进展

Logic-gated drug delivery systems in cancer immunotherapy

免疫治疗已经逐渐成为癌症治疗的主流疗法之一。然而,由于肿瘤免疫抑制的生理环境,导致免疫细胞抗原的提取呈递能力较弱,细胞毒性T细胞的浸润激活不充分。并且,患者的个体差异和缺乏靶向的治疗分布会引发过度免疫激活或免疫抑制等不良反应,导致免疫疗法对实体瘤的治疗效果并不理想。近年来,有许多学者将聚合物、核酸、细胞等具有根据信号输入进行逻辑处理能力的单元设计成免疫疗法的平台,使治疗平台在靶向肿瘤部位后,根据多种来自肿瘤微环境或外界信号输入进行逻辑处理,来达到时空可控的治疗目的。本文简要概述了基于合成纳米载体、核酸和嵌合抗原受体T细胞设计的逻辑门控治疗平台和其在肿瘤免疫治疗中的研究进展,并对各类平台的优缺点进行了总结和展望。

Immunotherapy has become a mainstream treatment for cancer.However,the immunosuppressive tumor microenvironment hinders the antigen extraction and presentation by immune cells,resulting in insufficient infiltration and activation of cytotoxic T cells.Moreover,patient variability and the systemic distribution of immunotherapeutic agents can cause toxic side effects,such as excessive activation or immunosuppression.The extratumoral toxicity and challenges in penetrating the tumor microenvironment hinder the effectiveness of immunotherapy on solid tumors.Recently,researchers have developed immunotherapy platforms using polymers,nucleic acids,and cells capable of logical processing based on signal inputs.These platforms can target tumors and perform logical processing based on various inputs from the tumor microenvironment or external signals.This review briefly introduces logic-gated platforms designed using synthetic nanocarriers,nucleic acids,and chimeric antigen receptor T-cells(CAR-T)and discusses research progress in immunotherapy,aiming to provide foresight by comparing the advantages and disadvantages of each platform.