Alkaline phosphatase-triggered assembly of etoposide enhances its anticancer effect
2018
Kiran, Sonia | Hai, Zijuan | Ding, Zhanling | Wang, Lin | Liu, Yaling | Zhang, Huafeng | Liang, Gaolin
Etoposide is a cancer-targeting drug but an overdose of etoposide leads to immunosuppression in patients. Therefore, the development of a new strategy to enhance its anticancer effect, while in the meantime alleviating its adverse effects, is important but challenging. In this work, with the assistance of a hydrogelator precursor Nap-Phe-Phe-Tyr(H₂PO₃)-OH (1P), etoposide phosphate (EP) was subjected to alkaline phosphatase (ALP)-triggered assembly, which obviously enhanced its anticancer efficacy in vitro and in vivo. In vitro tests indicated that the assembly of EP with 1P resulted in a slow release of etoposide and long-term inhibitory effects on HeLa cells. In vivo experiments indicated that, compared with those of EP-treated mice, the tumor growth of EP + 1P-treated mice was further inhibited while their body weight loss was alleviated. We envision that our hydrogelator-assisted assembly strategy could be applied to enhance the therapeutic effects of more drugs, while in the meantime alleviating their adverse effects in the future.
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