journal article·2024-02-08

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

Yandong Wang, Haodong Li, Guiming Niu, Yutang Li, Zhaoqin Huang, Shiqing Cheng, Keqin Zhang, Hui Li, Qiang Fu, Yanyan Jiang

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Abstract

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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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Photoacoustic and Ultrasonic Imaging · Ultrasound and Hyperthermia Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory for Liquid−Solid Structural Evolution & Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan, Shandong 250061, P. R. China

Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P. R. China

Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China

Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China

Key Laboratory of Urinary Diseases in Universities of Shandong, Shandong First Medical University, Jinan, Shandong 250021, P. R. China

Engineering Laboratory of Urinary Organ and Functional Reconstruction of Shandong Province, Jinan, Shandong 250021, P. R. China

Funding

National Natural Science Foundation of China · Jinan Science and Technology Bureau · The new material demonstration platform construction project from the Ministry of Industry and Information Technology · Special Funding of the Qilu Young Scholar Program of Shandong University · Taishan Scholars Program of Shandong Province

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