Composite Hydrogel for Spatiotemporal Lipid Intervention of Tumor Milieu

Author:

Ma Jia12,Guo Daoxia2,Ji Xiaoyuan2ORCID,Zhou Yanfeng2,Liu Chang2,Li Qian3,Zhang Jiye1,Fan Chunhai3,Song Haiyun2ORCID

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

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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