Alkaline phosphatase-triggered assembly of etoposide enhances its anticancer effect
Alkaline phosphatase-triggered assembly of etoposide enhances its anticancer effect
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碱性磷酸酶触发的依托泊苷组装增强其抗癌作用
DOI：
10.1039/c7cc09365a
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发表时间：
2018-02-21
影响因子：
4.9
通讯作者：
Liang, Gaolin
中科院分区：
文献类型：
--
作者：
Kiran, Sonia;Hai, Zijuan;Liang, Gaolin
依托泊苷是一种癌症靶向药物，但过量服用依托泊苷会导致患者免疫抑制。因此，开发一种新的策略来增强其抗癌作用，同时减轻其副作用，是重要但具有挑战性的。在这项工作中，在水凝胶前体Nap-Phe-PheTyr(H2PO3)-OH (1P)的帮助下，磷酸依托泊苷(EP)进行碱性磷酸酶(ALP)触发的组装，明显增强了其体外和体内的抗癌功效。体外试验表明，EP与1P的组装导致依托泊苷缓慢释放，并对HeLa细胞产生长期抑制作用。体内实验表明，与EP处理的小鼠相比，EP+1P处理的小鼠的肿瘤生长进一步受到抑制，体重减轻也得到缓解。我们设想，我们的水凝胶辅助组装策略可以应用于增强更多药物的治疗效果，同时减轻它们在未来的副作用。
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-PheTyr(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.