Biogenic platinum nanoparticles on bacterial fragments for enhanced radiotherapy to boost antitumor immunity
Zheng Deng, Jiawei Liu, Min Xi, Chunjie Wang, Huapan Fang, Xirui Wu, Cai Zhang, Guanting Sun, Yifan Zhang, Lin Shen, Minjiang Chen, Jiansong Ji, Zhuang Liu, Guangbao Yang
Abstract
Being widely utilized in clinic to treat solid tumors, the efficacy of radiotherapy (RT) is usually restricted by insufficient deposition of radiation energy and hypoxia-associated tumor radio-resistance. Moreover, as a local treatment technique, RT is ineffective against tumor metastases, the main cause of cancer death. Herein, biogenic platinum nanoparticles (Pt NPs) are in situ synthesized on the surface of Shewanella oneidensis MR-1 (S. oneidensis MR-1), followed by sonication to acquire Pt NPs decorated membrane fragments (PtMFs) for reinforcing the treatment outcome of RT. Thanks to the high-Z element intrinsic property and the catalytic property of Pt NPs in decomposing tumor endogenous H2O2 to produce oxygen, PtMFs not only effectively amplify radiation-induced DNA damages, but also significantly enhance tumor oxygenation to overcome the hypoxia-induced radio-resistance and reprogram the immunosuppressive tumor microenvironment, thereby enhancing antitumor efficacy in vivo. After PtMFs-mediated RT to trigger the immunogenic cell death (ICD), the generated tumor antigens subsequently elicit potent anti-tumor immune responses in the presence of bacterial membrane fragments as natural immunologic adjuvants. Via combination with programmed death-ligand 1 (PD-L1) checkpoint blockade, strong abscopal effects are achieved to effectively inhibit tumor metastases, whereas a long-term immune memory effect to reject rechallenged tumors is further observed. Therefore, such biogenic Pt-based therapeutic platforms present a unique approach for enhanced RT to inhibit tumor metastasis and recurrence by triggering strong anti-tumor immunity.