Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, P. R. China.
ACS Appl Mater Interfaces. 2024 Sep 11;16(36):47325-47336. doi: 10.1021/acsami.4c11418. Epub 2024 Aug 27.
Herein, we developed a paclitaxel prodrug (PSFc) through the conjugation of paclitaxel (PTX) and ferrocene a redox-responsive disulfide bond. PSFc displays acid-enhanced catalytic activity of Fenton reaction and is capable of forming stable nanoparticles (PSFc NPs) through the assembly with distearoyl phosphoethanolamine-PEG. After being endocytosed, PSFc NPs could release PTX to promote cell apoptosis in response to overexpressed redox-active species of tumor cells. Meanwhile, the ferrocene-mediated Fenton reaction promotes intracellular accumulation of hydroxyl radicals and depletion of glutathione, thus leading to ferroptosis. Compared with the clinically used Taxol, PSFc NPs exhibited more potent antitumor outcomes through the combined effect of chemotherapy and ferroptosis. This study may offer insight into a facile design of a prodrug integrating different tumor treatment methods for combating malignant tumors.
在此，我们通过将紫杉醇（PTX）和二茂铁连接，构建了一种紫杉醇前药（PSFc），其中包含一个氧化还原响应的二硫键。PSFc 表现出酸增强的芬顿反应催化活性，并能够通过与二硬脂酰基磷脂酰乙醇胺-聚乙二醇的组装形成稳定的纳米颗粒（PSFc NPs）。被内吞后，PSFc NPs 能够释放 PTX 以响应肿瘤细胞中过表达的氧化还原活性物质促进细胞凋亡。同时，二茂铁介导的芬顿反应促进了羟基自由基在细胞内的积累和谷胱甘肽的耗竭，从而导致铁死亡。与临床上使用的 Taxol 相比，PSFc NPs 通过化疗和铁死亡的联合作用表现出更强的抗肿瘤效果。这项研究可能为设计一种将不同肿瘤治疗方法结合在一起的前药提供了思路，以对抗恶性肿瘤。
