College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, China.
State Key Laboratory for Powder Metallurgy, Central South University, Changsha, Hunan, 410083, China.
Angew Chem Int Ed Engl. 2019 Nov 25;58(48):17425-17432. doi: 10.1002/anie.201909729. Epub 2019 Oct 22.
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. Cu Te nanoparticles exhibit tunable enzyme-mimicking activity (including glutathione oxidase and peroxidase) under near-infrared-II (NIR-II) light. The cascade reactions catalyzed by the Cu Te artificial enzyme gradually elevates intratumor oxidative stress to induce immunogenic cell death. Meanwhile, the continuously generated oxidative stress by the Cu Te 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 Cu Te artificial enzyme to suppress tumor relapse.
当前的癌症疗法受到肿瘤转移和复发的严重挑战。一种有前途的解决方案是建立抗肿瘤免疫。然而，免疫治疗的疗效受到肿瘤免疫抑制状态的高度阻碍。在这里提出了一种新的策略，即基于人工酶的催化免疫疗法。CuTe 纳米粒子在近红外-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）。CuTe 人工酶催化的级联反应逐渐增加肿瘤内氧化应激，诱导免疫原性细胞死亡。同时，CuTe 人工酶不断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反应，以根除原发性和远处转移性肿瘤。此外，在用 CuTe 人工酶治疗后成功获得了免疫记忆效应，以抑制肿瘤复发。
