体内
阿霉素
细胞毒性
毒性
化学
谷胱甘肽
体外
达皮
药理学
聚己内酯
生物化学
细胞凋亡
化疗
生物
酶
生物技术
有机化学
聚合物
遗传学
作者
Yongli Shi,Xueyan Hou,Shasha Yu,Xiaofei Pan,Mingbo Yang,Jie Hu,Xiao Wang
标识
DOI:10.1016/j.colsurfb.2022.112874
摘要
Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4', 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues.
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