前药
谷胱甘肽
化学
毒性
活性氧
癌细胞
细胞凋亡
药理学
酶
生物化学
癌症
生物
有机化学
遗传学
作者
Yu Zhou,Chengyu Zhang,Yuefei Wang,Jiaxing Zhang,Xiaohui Yan,Shengping You,Wei Qi,Rongxin Su,Zhimin He
标识
DOI:10.1016/j.colsurfb.2022.112853
摘要
Nanotechnology has been widely used in cancer treatment but only a small fraction (0.7 %) of the administered nanoparticle was delivered into a solid tumor, while the remaining fraction causes off-target toxicity in healthy tissues. The activation of prodrugs by exogenous enzymes can be used as an effective anticancer strategy to reduce systemic toxicity. In this study, the [email protected] imidazolate framework-8 ([email protected]) enzyme-activated prodrug system was created based on the high catalytic activity of LA in an acidic environment and the pH response (pH∼5.5) of ZIF-8. Quercetin (QU) was selected as the prodrug, which is non-toxic and even beneficial without being activated by LA. LA could be precisely released in the acidic tumor microenvironment for activating nontoxic QU successfully to produce toxic oxidized quercetin (OQU), and the LA was steady loaded on the [email protected] under physiological conditions (pH∼7.4). Especially, the high concentrations of glutathione (GSH) in tumors could accelerate the oxidation of QU by LA. Meanwhile, GSH could be consumed continuously by the reduction of OQU for regenerating QU, thus a LA-QU-GSH redox was formed ingeniously. Therefore, the synergistic effect of OQU toxicity and GSH depletion induced reactive oxygen species (ROS) accumulation and tumor cell apoptosis. Overall, the [email protected] prodrug system provides ideas for safe and effective cancer treatment with low off-target toxicity.
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