Affiliation:
1. Department of Nuclear Medicine Ruijin Hospital School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200030 China
2. State Key Laboratory for Oncogenes and Related Genes School of Biomedical Engineering Institute of Medical Robotics and Med‐X Research Institute Shanghai Jiao Tong University Shanghai 200030 China
3. Shanghai Key Laboratory of Gynecologic Oncology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China
4. Cancer Institute The Affiliated Hospital of Qingdao University Qingdao 266003 China
Abstract
AbstractAltered metabolism of cancer cells reshapes the unique tumor microenvironment (TME) with glucose addiction and high antioxidant levels, resulting in a strong alliance to promote tumor progression and treatment failure. Herein, a Pd/Pt/Au tri‐metallic mesoporous nanoparticle coated with pH‐responsive tannic acid‐iron ion (FeIIITA) network (PdPtAu@TF) is fabricated, aiming at reinforcing radioimmunotherapy by reprogramming nutrients and redox metabolisms. PdPtAu@TF has a fine hierarchical structure and demonstrates high glucose oxidase, peroxidase‐, catalase‐ and glutathione peroxidase‐mimic activities, acting as a self‐enhancing nanoreactor to consume endogenous glucose and break redox homeostasis in the harsh TME. As a result, cancer cells accelerate the uptake of lipids, especially polyunsaturated fatty acids when glucose is deficient, and then fall into lipid peroxidation‐induced ferroptosis trap to sensitize radiotherapy (RT), inhibiting tumor progression. More significantly, combined treatment with PdPtAu@TF can promote the polarization of pro‐inflammatory M1‐type macrophages as well as inhibit the proliferation of cancer‐associated fibroblasts to overcome RT‐induced immunosuppression and eliminate excessive tissue fibrosis, thereby eliciting antitumor immunity and suppressing tumor metastasis. Consequently, this study describes a promising strategy to enhance the efficacy of radioimmunotherapy by reprogramming tumor nutrients and redox metabolisms, which has great potential to benefit cancer treatments.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
8 articles.
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