Artificial Enzyme Catalyzed Cascade Reactions: Antitumor Immunotherapy Reinforced by NIR-II Light
Artificial Enzyme Catalyzed Cascade Reactions: Antitumor Immunotherapy Reinforced by NIR-II Light
复制标题
人工酶催化级联反应：NIR-II 光增强的抗肿瘤免疫疗法
DOI：
10.1002/anie.201909729
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发表时间：
2019-10-22
影响因子：
16.6
通讯作者：
Liu, You-Nian
中科院分区：
文献类型：
--
作者：
Wen, Mei;Ouyang, Jiang;Liu, You-Nian
肿瘤的转移和复发严重挑战了当前的癌症治疗。这些问题的一个有希望的解决方案是建立抗肿瘤免疫。然而，肿瘤的免疫抑制状态高度阻碍了免疫功效。这里提出了一种新的策略，基于人工酶的催化免疫疗法。Cu 2-xTe纳米颗粒在近红外II（NIR-II）光下表现出可调的酶模拟活性（包括谷胱甘肽氧化酶和过氧化物酶）。由Cu 2-xTe人工酶催化的级联反应逐渐升高肿瘤内氧化应激以诱导免疫原性细胞死亡。同时，由Cu 2-xTe人工酶持续产生的氧化应激逆转了免疫抑制性肿瘤微环境，并增强了抗肿瘤免疫应答，以根除原发性和远处转移性肿瘤。此外，在用Cu 2-xTe人工酶治疗后成功获得免疫记忆效应以抑制肿瘤复发。
Current cancer therapy is seriously challenged by tumor metastasis and recurrence. One promising solution to these problems is to build antitumor immunity. However, immunotherapeutic efficacy is highly impeded by the immunosuppressive state of the tumors. Here a new strategy is presented, catalytic immunotherapy based on artificial enzymes. Cu2-xTe nanoparticles exhibit tunable enzyme-mimicking activity (including glutathione oxidase and peroxidase) under near-infrared-II (NIR-II) light. The cascade reactions catalyzed by the Cu2-xTe artificial enzyme gradually elevates intratumor oxidative stress to induce immunogenic cell death. Meanwhile, the continuously generated oxidative stress by the Cu2-xTe artificial enzyme reverses the immunosuppressive tumor microenvironment, and boosts antitumor immune responses to eradicate both primary and distant metastatic tumors. Moreover, immunological memory effect is successfully acquired after treatment with the Cu2-xTe artificial enzyme to suppress tumor relapse.