肿瘤微环境
光动力疗法
免疫疗法
吲哚青绿
癌症研究
免疫系统
光敏剂
化学
免疫原性细胞死亡
药物输送
T细胞
医学
活性氧
药理学
免疫学
病理
生物化学
有机化学
作者
Xu Liu,Junlei Zhang,Xuemeng Guo,Jiaxin Huang,Zhanghua Lou,Xiaoqi Zhao,Qing Lin,Xiang Li,Jian You,Lihua Luo
标识
DOI:10.1016/j.jconrel.2023.10.037
摘要
Photo-immunotherapy is a promising strategy for the treatment of malignancies; however, its efficacy is often limited by the low tumor immunogenicity and immunosuppressive tumor microenvironment (TME). TME is typically deficient in L-arginine (L-Arg), which negatively impacts T cell survival and function. To address this issue, we developed a novel drug delivery system based on the multi-vesicular liposomes (MVLs) loaded with photosensitizer indocyanine green (ICG) and L-Arg (R), named R-ICG@MVLs. Under near-infrared (NIR) light irradiation, the PDT-mediated cascade reaction of reactive oxygen species (ROS) could oxidize a portion of L-Arg to generate NO, thereby inducing immunogenic tumor cell death (ITCD) and stimulating anti-tumor immune responses, including antigen-presenting cells (APCs) recruitment and T cells activation. Subsequently, R-ICG@MVLs continued to release L-Arg, which improved the immunosuppressive TME, providing nutritional support for the tumor-infiltrating T cells and thus enhancing their anti-tumor efficacy. Additionally, the photo-thermal effect of ICG could accelerate the membrane rearrangement of R-ICG@MVLs and produce multiple drug-loaded nanovesicles, thus enabling the NIR-controlled accelerated drug release. The formation of drug-loaded nanovesicles led to deeper penetration and widened the range of ICD and TME improvement, achieving a “shrapnel effect”. In conclusion, our strategy realized the dual effects of immune activation and nutrition support, which might provide a clinically applicable reference for tumor immunotherapy.
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