Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
Beijing Synchrotron Radiation Facility Institute of High Energy Physics Chinese Academy of Sciences, Beijing 100049, China.
J Am Chem Soc. 2023 Jun 14;145(23):12586-12600. doi: 10.1021/jacs.3c01532. Epub 2023 Jun 5.
Nanozymes have shown great promise in reactive oxygen species (ROS)-mediated tumor therapy with mitigated side effects but are normally limited by the complex tumor microenvironment (TME). Herein, to overcome the adverse effects of TME, such as tumor hypoxia and high endogenous glutathione (GSH), an aptamer-functionalized Pd@MoO nano-hydrangea (A-Pd@MoO NH) is constructed for high-efficiency cancer therapy. Utilizing the irregular shape characteristics of nano Pd, the A-Pd@MoO NH nanozyme simultaneously exposes catalase-like Pd(111) and oxidase-like Pd(100) surface facets as dual active centers. This can catalyze cascade enzymatic reactions to overcome the negative effects of tumor hypoxia caused by the accumulation of cytotoxic superoxide (O) radicals in TME without any external stimuli. In addition, the nanozyme can effectively degrade the overexpressed glutathione (GSH) through the redox reaction to avoid nontherapeutic consumption of O radicals. More significantly, as a reversible electron station, MoO can extract electrons from HO decomposing on Pd(111) or GSH degradation and transfer them back to Pd(100) through oxygen bridges or few Mo-Pd bonds. This can synergistically enhance enzyme-like activities of dual active centers and the GSH-degrading ability to enrich O radicals. In this way, the A-Pd@MoO NH nanozyme can selectively and remarkably kill tumor cells while keeping the normal cell line unharmed.
纳米酶在活性氧（ROS）介导的肿瘤治疗中显示出巨大的应用潜力，可减轻副作用，但通常受到复杂的肿瘤微环境（TME）的限制。在此，为了克服 TME 的不利影响，例如肿瘤缺氧和高内源性谷胱甘肽（GSH），构建了一种适体功能化的 Pd@MoO 纳米绣球花（A-Pd@MoO NH），用于高效癌症治疗。利用纳米 Pd 的不规则形状特征，A-Pd@MoO NH 纳米酶同时暴露类过氧化氢酶的 Pd(111)和类氧化酶的 Pd(100)表面晶面作为双活性中心。这可以催化级联酶反应，克服 TME 中细胞毒性超氧自由基（O）积累引起的肿瘤缺氧的负面影响，而无需任何外部刺激。此外，纳米酶可以通过氧化还原反应有效降解过表达的谷胱甘肽（GSH），以避免 O 自由基的非治疗性消耗。更重要的是，作为一种可逆的电子站，MoO 可以从 Pd(111)上分解的 HO 或 GSH 降解中提取电子，并通过氧桥或少量 Mo-Pd 键将它们转移回 Pd(100)。这可以协同增强双活性中心的酶样活性和 GSH 降解能力，以富集 O 自由基。这样，A-Pd@MoO NH 纳米酶可以选择性地显著杀死肿瘤细胞，同时保持正常细胞系不受伤害。
