谷胱甘肽
过氧化氢
化学
激进的
介孔二氧化硅
内吞作用
细胞内
过氧化氢酶
生物物理学
抗氧化剂
活性氧
基质(水族馆)
生物化学
介孔材料
酶
催化作用
细胞
生物
生态学
作者
Ling Jing,Binghua Wang,Xia‐Nan Li,Rui Zhang,Pan Lu,Han Zhang,Yeting Hu,Shi‐ BoWang,Xiangdong Kong
标识
DOI:10.1002/ppsc.202300054
摘要
Abstract Chemodynamic therapy (CDT) is a promising method that uses endogenous hydrogen peroxide (H 2 O 2 ) to produce cytotoxic hydroxyl radicals (•OH) via Fenton reaction to kill tumor cells. However, the insufficient contents of H 2 O 2 and the presence of glutathione (GSH) can significantly reduce the therapeutic effect of CDT. Herein, a multifunctional nanoregulator (3‐AT&MA@FHM) that combines Fe‐doped hollow mesoporous silica nanoparticles (Fe‐doped hMSN, or FHM) with 3‐amino‐1,2,4‐triazole (3‐AT) and maleimide (MA) are developed to overcome these challenges. After endocytosis by tumor cells, FHM part of the nanoregulator degrades in a mildly acidic intracellular environment and releases Fe 3+ for CDT. The subsequently released 3‐AT serves as a catalase inhibitor to promote the accumulation of H 2 O 2, while MA acts as a GSH scavenger to decrease the GSH content in tumor cells. This multifunctional nanoplatform simultaneously regulates the contents of H 2 O 2 ‐the substrate for Fenton reaction and GSH‐the main antioxidant, resulting in a significantly enhanced CDT effect. Moreover, organoids are used for safety and toxicity evaluation. The results of organoids experiments showed similar trends to those of cellular experiments, but MIO is more resistant to stress than cells. This study is expected to provide a novel idea for the design of highly efficient CDT nanosystems.
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