Ultrasmall nanostructured drug based pH-sensitive liposome for effective treatment of drug-resistant tumor

【作者】Yanyan Li, Yongxia Zhai, Wei Liu, Kaixiang Zhang, Junjie Liu , Jinjin Shiand Zhenzhong Zhang

【期刊名】Journal of Nanobiotechnology

【影响因子】 2019年:5.35

【作者单位】School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2019, 17: 117

【关键词】Reversing drug resistance, Drug efflux, Nuclear-transport, Nanostructured drug, Programmatic release

【摘要】Background: Cancer cells always develop ways to resist and evade chemotherapy. To overcome this obstacle, herein,we introduce a programmatic release drug delivery system that imparts avoiding drug efflux and nuclear transport insynchrony via a simple nanostructured drug strategy.Results: The programmatic liposome-based nanostructured drugs (LNSD) contained two modules: doxorubicin(DOX) loaded into tetrahedral DNA (TD, ~ 10 nm) to form small nanostructured DOX, and the nanostructured DOXwas encapsulated into the pH-sensitive liposomes. In the in vitro and in vivo studies, LNSD shows multiple benefits fordrug resistance tumor treatment: (1) not only enhanced the cellular DOX uptake, but also maintained DOX concentration in an optimum level in resistant tumor cells via nanostructure induced anti-efflux effect; (2) small nanostructuredDOX efficiently entered into cell nuclear via size depended nuclear-transport for enhanced treatment; (3) improvedthe pharmacokinetics and biodistribution via reducing DOX leakage during circulation.Conclusions: The system developed in this study has the potential to provide new therapies for drug-resistant

tumor.

【全文链接】https://doi.org/10.1186/s12951-019-0550-7