上睑下垂
ESCRT公司
内体
免疫系统
细胞生物学
纳米载体
化学
细胞
程序性细胞死亡
癌症研究
细胞凋亡
药物输送
医学
免疫学
生物
生物化学
有机化学
作者
Zhaoting Li,Fanyi Mo,Yixin Wang,Wen Li,Yu Chen,Jun Li,Ting‐Jing Chen‐Mayfield,Quanyin Hu
标识
DOI:10.1038/s41467-022-34036-8
摘要
Pore-forming Gasdermin protein-induced pyroptosis in tumor cells promotes anti-tumor immune response through the release of pro-inflammatory cytokines and immunogenic substances after cell rupture. However, endosomal sorting complexes required for transport (ESCRT) III-mediated cell membrane repair significantly diminishes the tumor cell pyroptosis by repairing and subsequently removing gasdermin pores. Here, we show that blocking calcium influx-triggered ESCRT III-dependent membrane repair through a biodegradable nanoparticle-mediated sustained release of calcium chelator (EI-NP) strongly enhances the intracellularly delivered GSDMD-induced tumor pyroptosis via a bacteria-based delivery system (VNP-GD). An injectable hydrogel and a lyophilized hydrogel-based cell patch are developed for peritumoral administration for treating primary and metastatic tumors, and implantation for treating inoperable tumors respectively. The hydrogels, functioning as the local therapeutic reservoirs, can sustainedly release VNP-GD to effectively trigger tumor pyroptosis and EI-NP to prevent the ESCRT III-induced plasma membrane repair to boost the pyroptosis effects, working synergistically to augment the anti-tumor immune response.
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