MnO2-Based Nanomotors with Active Fenton-like Mn2+ Delivery for Enhanced Chemodynamic Therapy
MnO2-Based Nanomotors with Active Fenton-like Mn2+ Delivery for Enhanced Chemodynamic Therapy
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基于 MnO2 的纳米马达，具有活性类芬顿 Mn2 输送，用于增强化学动力学治疗
DOI：
10.1021/acsami.1c08926
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发表时间：
2021-08-09
影响因子：
9.5
通讯作者：
Tu, Yingfeng
中科院分区：
文献类型：
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作者：
Ou, Juanfeng;Tian, Hao;Tu, Yingfeng
化学动力疗法（Chemodynamic therapy， CDT）是一种基于Fenton化学的新兴癌症治疗策略，它可以将内源性H2O2转化为有毒的中心点OH。然而，由于被动CDT纳米药物的内吞作用有限，穿透能力低，导致其抗癌效果不理想。在此，我们提出了一种基于中空二氧化锰纳米粒子的自推进可生物降解纳米马达系统的成功制造，该系统具有催化活性，可用于活性Fenton-like Mn2+的传递和增强CDT。与被动式纳米马达相比，纳米马达在二维细胞培养系统和三维肿瘤多细胞球体中均具有显著提高的穿透性和增强的扩散。在细胞内摄取纳米运动后，通过消耗过表达的细胞内谷胱甘肽（GSH）大量产生有毒的fenton样Mn2+， GSH对中心点OH具有强大的清除作用，从而导致癌症CDT增强。基于二氧化锰的纳米运动系统具有增强的穿透能力和内源性GSH清除能力，在不久的将来有望成为癌症治疗的潜在平台。
Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2 into toxic center dot OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2 nanoparticles with catalytic activity for active Fenton-like Mn2+ delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+ is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on center dot OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.