Affiliation:
1. Department of Orthopaedic Surgery Zhongshan Hospital Fudan University Shanghai 200032 P. R. China
2. Department of Orthopaedic Surgery Zhongshan Hospital (Xiamen) Fudan University Xiamen 361015 P. R. China
3. Materdicine Lab School of Life Sciences Shanghai University Shanghai 200444 P. R. China
Abstract
AbstractDespite recent advancements in cancer immunotherapy, challenges have yet to be surmounted to achieve two major goals of magnifying antitumor immunity and remodeling the immunosuppressive tumor microenvironment. Here, a nanosystem (ODM‐R) that integrates oxygen‐deficient molybdenum oxide (ODM) nanosonosensitizers and R7 peptides with tumor metabolism regulation effects is designed and fabricated for synergistic sonodynamic–immunometabolic therapy of spinal‐metastasized tumors. The ODM generates reactive oxygen species upon ultrasound irradiation to implement sonodynamic therapy (SDT), inducing cancer cell apoptosis and immunogenic cell death. The R7 attached on ODM markedly inhibits the uptake of glucose and excretion of lactic acid in cancer cells by perturbing the glycolysis process. The combination of SDT and tumor glycolysis obstruction by ODM‐R guarantees satisfactory efficacy in synergizing with PD‐L1 antibody to eradicate spinal‐metastasized tumors, achieving concurrent sonodynamic‐triggered immune activation and immunosuppressive tumor microenvironment remodeling. This work provides a proof‐of‐concept of nanosonosensitizers for boosting cancer immunotherapy by SDT and tumor metabolic regulation.
Funder
National Natural Science Foundation of China
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
5 articles.
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