MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
International Research Center for X Polymers, International Campus, Zhejiang University, Haining 314400, People's Republic of China.
ACS Nano. 2023 Aug 22;17(16):15713-15723. doi: 10.1021/acsnano.3c02964. Epub 2023 Aug 11.
Chemodynamic therapy (CDT) has emerged as a promising strategy for cancer treatment. However, its effectiveness has been hindered by insufficient hydrogen peroxide (HO) and high reductive glutathione (GSH) within tumors, which are the two main reasons for the inefficiency of Fenton/Fenton-like reaction-based CDT. Herein, we present a HO boost-GSH depletion strategy for enhanced CDT to fight against melanoma through a microneedle (MN)-based transcutaneous delivery method. The MN system is composed of dissolvable polyvinylpyrrolidone integrated with stimuli-responsive prodrugs. Under an intracellular acidic environment, the smart release of HO boosting components is triggered, subsequently initiating nitric oxide (NO) release and enhancing the Fenton-like reaction in a cascade manner. The generation of hydroxyl radicals (OH), along with the depletion of GSH by NO, amplifies the oxidative stress within tumor cells, promoting apoptosis and ferroptosis. The antitumor efficacy of the MN patch is validated in an A375 mouse melanoma model. This "HO boost-GSH depletion-Fenton killing" strategy expands the options for superficial tumor treatment through MN-mediated enhanced CDT.
化学动力学疗法（CDT）已成为癌症治疗的一种有前途的策略。然而，其疗效受到肿瘤内过氧化氢（HO）和还原型谷胱甘肽（GSH）含量不足的限制，这是基于芬顿/类芬顿反应的 CDT 效率低下的两个主要原因。在此，我们提出了一种通过基于微针（MN）的经皮给药方法增强 CDT 以对抗黑色素瘤的 HO 提升-GSH 耗竭策略。MN 系统由可溶解的聚乙烯吡咯烷酮与响应性前药集成。在细胞内酸性环境下，智能触发 HO 提升成分的释放，随后以级联方式引发一氧化氮（NO）的释放并增强类芬顿反应。羟基自由基（OH）的产生以及 NO 耗竭 GSH，放大了肿瘤细胞内的氧化应激，促进细胞凋亡和铁死亡。MN 贴片在 A375 小鼠黑色素瘤模型中的抗肿瘤功效得到了验证。这种“HO 提升-GSH 耗竭-Fenton 杀伤”策略通过 MN 介导的增强 CDT 为浅表肿瘤治疗提供了更多选择。
