Key Laboratory for Analytical Science of Food Safety and Biology of the MOE, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350116, P. R. China.
Department of Neurosurgery, Fujian Medical University Union Hospital, Neurosurgical Institute of Fujian Province, Fuzhou, 350001, P.R. China.
Biomater Sci. 2022 May 17;10(10):2673-2680. doi: 10.1039/d1bm01940f.
Responsive nano-drug delivery systems, especially multi-responsive systems, based on the complex characteristics of the tumor microenvironment (TME), such as acidic pH, hypoxia, and hydrogen peroxide (HO) overexpression, could enhance the biological activity of the drugs and reduce the side effects. In this study, a HO/glutathione (GSH) procedurally activatable nanoplatform (CuS-PEG/DOX NSs) was prepared as a vector of drugs released by responsive morphologic transformation and the co-activated Fenton agent for tumor-specific synergistic therapy. After endocytosis into tumor cells, CuS-PEG/DOX NSs were initially oxidized by over-expressed HO and transformed from nanosheets to nanoflowers, leading to the release of doxorubicin (DOX). Subsequently, CuS nanoflowers (CuS NFs) reacted with the local GSH, liberated a large number of copper ions, and induced GSH depletion. The released DOX promoted the generation of intracellular HO through cascade reactions, which were further utilized to facilitate the release of DOX and generate toxic hydroxyl radicals (˙OH) a copper-based Fenton-like reaction. CuS-PEG/DOX NSs sequentially activated by HO and GSH in tumor cells exhibited relatively high cytotoxicity, whereas normal cells were still alive. This nanoplatform, as a procedurally activatable delivery system, may have excellent potential for tumor-specific synergistic therapy.
响应性纳米药物递送系统，特别是多响应系统，基于肿瘤微环境（TME）的复杂特征，如酸性 pH 值、缺氧和过表达的过氧化氢（HO），可以增强药物的生物活性并降低副作用。在本研究中，制备了一种 HO/谷胱甘肽（GSH）程序性激活的纳米平台（CuS-PEG/DOX NSs），作为通过响应形态转化和共激活的 Fenton 试剂释放的药物的载体，用于肿瘤特异性协同治疗。进入肿瘤细胞后，CuS-PEG/DOX NSs 最初被过表达的 HO 氧化，并从纳米片转变为纳米花，导致阿霉素（DOX）的释放。随后，CuS 纳米花（CuS NFs）与局部 GSH 反应，释放大量铜离子，并诱导 GSH 耗竭。释放的 DOX 通过级联反应促进细胞内 HO 的产生，这进一步用于促进 DOX 的释放并产生有毒的羟基自由基（˙OH），这是一种基于铜的类 Fenton 反应。在肿瘤细胞中先后被 HO 和 GSH 激活的 CuS-PEG/DOX NSs 表现出相对较高的细胞毒性，而正常细胞仍然存活。这种纳米平台作为一种程序性激活的递送系统，可能具有用于肿瘤特异性协同治疗的巨大潜力。
