Tumor-Microenvironment-Responsive Cascade Reactions by a Cobalt-Single-Atom Nanozyme for Synergistic Nanocatalytic Chemotherapy
Tumor-Microenvironment-Responsive Cascade Reactions by a Cobalt-Single-Atom Nanozyme for Synergistic Nanocatalytic Chemotherapy
复制标题
钴-单原子纳米酶协同肿瘤微环境级联反应的研究
DOI：
10.1002/anie.202204502
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发表时间：
2022-09-02
影响因子：
16.6
通讯作者：
Chen, Chunying
中科院分区：
文献类型：
--
作者：
Cai, Shuangfei;Liu, Jiaming;Chen, Chunying
纳米催化疗法涉及纳米酶触发的肿瘤微环境（TME）中活性氧（ROS）的产生，已经在肿瘤治疗中显示出潜力，但是纳米酶仍然面临影响治疗功效的活性和特异性的挑战。在此，我们报告了一种基于单原子纳米酶的策略，以启动TME中的级联酶促反应，用于肿瘤特异性治疗。在N掺杂的多孔碳（Co-SAs@NC）上具有Co-N配位的钴单原子纳米酶显示出过氧化氢酶样活性，其分解细胞内源性H2 O2以产生O-2，以及随后的氧化酶样活性，其将O-2转化为细胞毒性超氧自由基以有效地杀死肿瘤细胞。通过与多柔比星结合，该疗法在体内实现了显著增强的抗肿瘤作用。我们的研究结果表明，级联TME特异性催化治疗联合化疗是一种有效的肿瘤治疗策略。
Nanocatalytic therapy, involving the nanozyme-triggered production of reactive oxygen species (ROS) in the tumor microenvironment (TME), has demonstrated potential in tumor therapy, but nanozymes still face challenges of activity and specificity that compromise the therapeutic efficacy. Herein, we report a strategy based on a single-atom nanozyme to initiate cascade enzymatic reactions in the TME for tumor-specific treatment. The cobalt-single-atom nanozyme, with Co-N coordination on N-doped porous carbon (Co-SAs@NC), displays catalase-like activity that decomposes cellular endogenous H2O2 to produce O-2, and subsequent oxidase-like activity that converts O-2 into cytotoxic superoxide radicals to efficiently kill tumor cells. By incorporation with doxorubicin, the therapy achieves a significantly enhanced antitumor effect in vivo. Our findings show that cascade TME-specific catalytic therapy combined with chemotherapy is a promising strategy for efficient tumor therapy.