Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy

利用微生物合成普鲁士蓝增强免疫检查点阻断疗法

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作者:Dongdong Wang # ,Jiawei Liu # ,Changlai Wang ,Weiyun Zhang ,Guangbao Yang ,Yun Chen ,Xiaodong Zhang ,Yinglong Wu ,Long Gu ,Hongzhong Chen ,Wei Yuan ,Xiaokai Chen ,Guofeng Liu ,Bin Gao ,Qianwang Chen ,Yanli Zhao

Abstract

Cancer 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.

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