Affiliation:
1. School of Pharmacy Health Science Center Xi'an Jiaotong University Xi'an 710061 P. R. China
2. State Key Laboratory of Oncogenes and Related Genes Center for Single‐Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine Shanghai 200025 P. R. China
3. School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine Shanghai Jiao Tong University Shanghai 200240 P. R. China
Abstract
AbstractInduction of immunogenic cell death (ICD) plays crucial roles in cancer immunotherapy, whereas its efficacy is severely compromised by redundant antioxidant defenses in cancer cells and aberrant lipid metabolism in immunosuppressive cell populations. In this work, it is found that hollow mesoporous CuS nanoparticles (NPs) possess an intrinsic capacity of inhibiting glutathione peroxidase 4 (GPX4). When loaded with an inhibitor of the ferroptosis suppressor protein 1 (FSP1), these NPs block two parallel redox systems and cooperate with near‐infrared irradiation to reinforce ICD. A hydrogel co‐delivering cancer‐cell‐targeting CuS NPs and immunosuppressive‐cell‐targeting sulfo‐N‐succinimidyl oleate (SSO) for spatiotemporal lipid intervention i further fabricated. While the CuS NPs augment ICD via synergistic lipid peroxidation, SSO reinstates immune perception via lipid metabolic reprogramming, thereby coordinately triggering robust innate and adaptive immunity to restrain tumor growth, relapse, and metastasis. This study provides an immunometabolic therapy via orchestrated lipid modulation in the tumor milieu.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Shanghai
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
23 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献