iProXProteomicsYanli ZhaoMus Musculushttp://www.iprox.org/page/project.html?id=IPX0005125000zhaoyanli@ntu.edu.sgNanyang Technological UniversityiProXCancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.Wang Dongdong D, Liu Jiawei J, Wang Changlai C, Zhang Weiyun W, Yang Guangbao G, Chen Yun Y, Zhang Xiaodong X, Wu Yinglong Y, Gu Long L, Chen Hongzhong H, Yuan Wei W, Chen Xiaokai X, Liu Guofeng G, Gao Bin B, Chen Qianwang Q, Zhao Yanli YfalseQuantitative proteomic analysis reveals the expression of various proteins in mice during the tumor treatmentBased on the gene ontology (GO) results, we found that proteins associated with responses or processes related to stimulus, immune system, signalling, cell killing, and antioxidant activity were more up-regulated after MiBaMc treatment. In contrast, proteins that related to cell integrity and cell growth were more down-regulated. Those results indicated that MiBaMc induced strengthened tumour damage, which should be attributed to the synergistic effect induced by hyperthermia and ROS. Furthermore, the prominent upregulation of proteins associated with antioxidant activity also directly indicated the enhanced oxidative pressure of tumours in the MiBaMc treated group. Specifically, there were obvious overlays between proteins associated with heat shock, oxidative stress, and cell death. Thus both photothermal-induced hyperthermia and photodynamic-induced oxidative damage contributed to immune cell death. Moreover, a significant enhancement in the protein level associated with immune response was observed from the GO analysis, suggesting the antitumour capacity should be attributed to the systemic immune activation of the MiBaMc. This phenomenon can also be verified from the prominent overlays between proteins associated with immune response, inflammation, and bacteria infection.Wed Sep 28 00:00:00 BST 2022PXD0370691009037221237