材料科学
内质网
免疫原性细胞死亡
未折叠蛋白反应
声动力疗法
免疫疗法
可生物降解聚合物
活性氧
细胞生物学
癌症研究
纳米技术
免疫系统
生物物理学
激酶
化学
程序性细胞死亡
蛋白激酶A
癌症免疫疗法
脂多糖
细胞凋亡
信号转导
癌细胞
胞浆
先天免疫系统
细胞
作者
Xiaowei Tong,Bingzheng Yu,Yajian Li,Meifang Shen,Tiejun Bing,Xiaomin Li,Haihua Xiao,Yingjie Yu
标识
DOI:10.1002/adfm.202516487
摘要
Abstract Sonodynamic therapy (SDT), which utilizes ultrasound (US) to activate sonosensitizers for generating reactive oxygen species (ROS), demonstrates significant potential in sonodynamic immunotherapy through triggering endoplasmic reticulum (ER) stress and subsequently activating immunogenic cell death (ICD). However, its clinical translation has been constrained by the poor biodegradability of most sonosensitizers. This study reports the first biodegradable pseudo‐conjugated polymeric sonosensitizer (PSP), exhibiting exceptional biodegradability and efficient ROS production. To further boost sonodynamic immunotherapy, a protein kinase R‐like endoplasmic reticulum kinase (PERK) inhibitor GSK2606414 (PERKi) is co‐assembled with PSP to form nanoparticles (PERKi NP). In a 4T1 cancer model, PERKi NP can generate substantial ROS to induce ER stress upon US irradiation. Notably, the generated ROS trigger the release of PERKi, which inhibit PERK pathway, thereby amplifying ER stress and ultimately activating ICD‐associated immune responses. Overall, PERKi NP offer a promising strategy for sonodynamic immunotherapy by amplifying ER stress to potentiate ICD‐mediated immune activation.
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