氧化应激
免疫原性细胞死亡
癌症免疫疗法
肿瘤微环境
免疫疗法
癌症研究
癌细胞
化学
前列腺癌
医学
免疫系统
生物化学
癌症
免疫学
内科学
作者
Yandong Wang,Haodong Li,Guiming Niu,Yutang Li,Zhaoqin Huang,Shiqing Cheng,Keqin Zhang,Hui Li,Qiang Fu,Yanyan Jiang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-02-08
被引量:4
标识
DOI:10.1021/acsnano.3c12511
摘要
Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S–S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8+ T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.
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