Tumor-activatable ultrasmall nanozyme generator for enhanced penetration and deep catalytic therapy
Tumor-activatable ultrasmall nanozyme generator for enhanced penetration and deep catalytic therapy
复制标题
可激活肿瘤的超小型纳米酶发生器，用于增强渗透和深层催化治疗
DOI：
10.1016/j.biomaterials.2020.120263
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发表时间：
2020-11-01
期刊：
影响因子：
14
通讯作者：
Qu, Xiaogang
中科院分区：
文献类型：
--
作者：
Liu, Xinping;Liu, Zhengwei;Qu, Xiaogang
肿瘤可激活的超小纳米酶的产生是一种前所未有的策略，以克服传统的活性氧（ROS）为基础的纳米药物的固有致命缺陷，用于深入肿瘤渗透，包括有限的组织穿透深度的外部能量，严重依赖于氧气和治疗剂的非特异性毒性。在这里，基于葡萄糖氧化酶（GOx）和嵌入酸可解离的沸石咪唑酯骨架-8（ZIF-8）中的超小过氧化物酶纳米酶之间的级联反应，这种肿瘤可活化的超小纳米酶发生器被设计用于增强渗透和深度催化治疗。在弱酸性肿瘤微环境的帮助下，由肿瘤内葡萄糖产生的葡萄糖酸可以逐渐诱导ZIF-8解离以释放具有显著肿瘤内穿透的超小过氧化物酶纳米酶。另一方面，所产生的具有相对长寿命的过氧化氢可随后被穿透的pemxidase纳米酶催化成毒性羟基自由基，用于深度催化治疗。通过这种方式，精心设计的纳米平台不仅可以大大增强肿瘤穿透，而且可以在没有氧气参与和外部能量输入的情况下直接诱导外源性ROS，从而彻底避免了传统的基于ROS的纳米药物在极度缺氧的肿瘤中心的失活，最终导致显着的深度催化治疗。
Tumor-activatable ultrasmall nanozyme generation is an unprecedented strategy to overcome intrinsically fatal defects of traditional reactive oxygen species (ROS)-based nanoagents for deep tumor penetration, including limited tissue-penetrating depth of external energy, heavy reliance on oxygen and nonspecific toxicity of therapeutic agents. Here, based on the cascade reaction between glucose oxidase (GOx) and ultrasmall peroxidase nanozyme embedded into acid-dissociable zeolitic imidazolate framework-8 (ZIF-8), such a tumor-activatable ultrasmall nanozyme generator is designed for enhanced penetration and deep catalytic therapy. With the aid of mildly acidic tumor microenvironment, the produced gluconic acid from intratumoral glucose can gradually induce the dissociation of ZIF-8 to release ultrasmall peroxidase nanozyme with significant intratumoral penetration. On the other hand, the generated hydrogen peroxide with relatively long-life can be subsequently catalyzed by penetrated pemxidase nanozyme into toxic hydroxyl radicals for deep catalytic therapy. In this way, the well-designed nanoplatform not only can greatly enhance tumor penetration but also directly induce exogenous ROS without oxygen participation and external energy input, thereby thoroughly avoiding the inactivation of traditional ROS-based nanoagents in the extremely hypoxic tumor center and finally resulting in remarkable deep catalytic therapy.