Reprogramming Dysfunctional Dendritic Cells by a Versatile Catalytic Dual Oxide Antigen-Captured Nanosponge for Remotely Enhancing Lung Metastasis Immunotherapy

利用多功能催化双氧化物抗原捕获纳米海绵重新编程功能失调的树突状细胞,以远程增强肺转移免疫治疗

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作者:Min-Ren Chiang, Chin-Wei Hsu, Wan-Chi Pan, Ngoc-Tri Tran, Yu-Sheng Lee, Wen-Hsuan Chiang, Yu-Chen Liu, Ya-Wen Chen, Shih-Hwa Chiou, Shang-Hsiu Hu

Abstract

Dendritic cells (DCs) play a crucial role in initiating antitumor immune responses. However, in the tumor environment, dendritic cells often exhibit impaired antigen presentation and adopt an immunosuppressive phenotype, which hinders their function and reduces their ability to efficiently present antigens. Here, a dual catalytic oxide nanosponge (DON) doubling as a remotely boosted catalyst and an inducer of programming DCs to program immune therapy is reported. Intravenous delivery of DON enhances tumor accumulation via the marginated target. At the tumor site, DON incorporates cerium oxide nanozyme (CeO2)-coated iron oxide nanocubes as a peroxide mimicry in cancer cells, promoting sustained ROS generation and depleting intracellular glutathione, i.e., chemodynamic therapy (CDT). Upon high-frequency magnetic field (HFMF) irradiation, CDT accelerates the decomposition of H2O2 and the subsequent production of more reactive oxygen species, known as Kelvin's force laws, which promote the cycle between Fe3+/Fe2+ and Ce3+/Ce4+ in a sustainable active surface. HFMF-boosted catalytic DON promotes tumors to release tumor-associated antigens, including neoantigens and damage-associated molecular patterns. Then, the porous DON acts as an antigen transporter to deliver autologous tumor-associated antigens to program DCs, resulting in sustained immune stimulation. Catalytic DON combined with the immune checkpoint inhibitor (anti-PD1) in lung metastases suppresses tumors and improves survival over 40 days.

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