Reactive oxygen species-responsive paclitaxel prodrug for image-guided treatment of breast cancer
Paclitaxel serves as a crucial active pharmaceutical ingredient with excellent effect in cancer treatment.However,it is limited by poor bioavailability and obvious side-effects.To alleviate this problem,a reactive oxygen species(ROS)-responsive fluorescent prodrug 2-(benzothiazol-2-yl)-6-methoxyphenol-thioketal-paclitaxel(BT-TK-PTX)was designed and synthesized in this study which could trigger the release of paclitaxel under the stimulation of hydrogen peroxide in tumor.The structure of this prodrug was confirmed by NMR and MS,and its optical performance(including fluorescence titration test,kinetic monitoring,selectivity and interference test),cytotoxicity and focused image were detected and analyzed.The results of spectroscopy showed that the prodrug BT-TK-PTX could be specifically activated by hydrogen peroxide and the fluorescence intensity increased by approximately 12 times.Cytotoxic test showed that the prodrug BT-TK-PTX could effectively mask the toxic and side effects of free drugs on normal cells,and could play a unique anti-cancer activity in tumor cells.Confocal imaging experiments showed that BT-TK-PTX could be gradually absorbed by cells,and the uptake process was also monitored.This study realizes the real-time monitoring of drug activation and action process by using the fluorescence,and confirms that the produrg BT-TK-PTX can obviously reduce the toxic and side effects of paclitaxel on normal cells.
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