Boosting Sono-immunotherapy of Prostate Carcinoma through Amplifying Domino-Effect of Mitochondrial Oxidative Stress Using Biodegradable Cascade-Targeting Nanocomposites

被引：13

作者：

Wang, Yandong ^{[1
]}

Li, Haodong ^{[2
]}

Niu, Guiming ^{[1
]}

Li, Yutang ^{[1
]}

Huang, Zhaoqin ^{[3
]}

Cheng, Shiqing ^{[4
]}

Zhang, Keqin ^{[2
]}

Li, Hui ^{[1
]}

Fu, Qiang ^{[2
,5
,6
]}

Jiang, Yanyan ^{[1
]}

机构：

[1] Shandong Univ, Sch Mat Sci & Engn, Key Lab Liquid Solid Struct Evolut & Proc Mat, Minist Educ, Jinan 250061, Shandong, Peoples R China

[2] Shandong Univ, Dept Urol, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China

[3] Shandong First Med Univ, Shandong Prov Hosp, Dept Radiol, Jinan 250021, Shandong, Peoples R China

[4] Shandong First Med Univ, Shandong Prov Hosp, Dept Clin Lab, Jinan 250021, Shandong, Peoples R China

[5] Shandong First Med Univ, Key Lab Urinary Dis Univ Shandong, Jinan 250021, Shandong, Peoples R China

[6] Engn Lab Urinary Organ & Funct Reconstruct Shandon, Jinan 250021, Shandong, Peoples R China

来源：

ACS NANO | 2024年 / 18卷 / 07期

基金：

中国国家自然科学基金;

关键词：

sono-immunotherapy; immunogeniccell death; cascade-targeting; reactive oxygen species; immuneresponse;

D O I：

10.1021/acsnano.3c12511

中图分类号：

O6 [化学];

学科分类号：

0703 ;

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.

引用

页码：5828 / 5846

页数：19