The Fifth Affiliated Hospital of Zhengzhou University, Kangfu Road, Zhengzhou, 450052, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
J Nanobiotechnology. 2019 Nov 29;17(1):117. doi: 10.1186/s12951-019-0550-7.
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 in synchrony via a simple nanostructured drug strategy.
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 DOX was encapsulated into the pH-sensitive liposomes. In the in vitro and in vivo studies, LNSD shows multiple benefits for drug 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 nanostructured DOX efficiently entered into cell nuclear via size depended nuclear-transport for enhanced treatment; (3) improved the pharmacokinetics and biodistribution via reducing DOX leakage during circulation.
The system developed in this study has the potential to provide new therapies for drug-resistant tumor.
癌细胞总是会发展出抵抗和逃避化疗的方法。为了克服这一障碍，本文介绍了一种程序性释放药物递送系统，该系统通过一种简单的纳米结构药物策略同步赋予避免药物外排和核转运的功能。
基于脂质体的程序性纳米结构药物（LNSD）包含两个模块：载有多柔比星（DOX）的四面体 DNA（TD，~10nm）形成小的纳米结构 DOX，并且纳米结构 DOX 被包裹在 pH 敏感的脂质体中。在体外和体内研究中，LNSD 为耐药肿瘤治疗带来了多种益处：（1）不仅增强了细胞摄取 DOX 的能力，而且通过纳米结构诱导的抗外排作用，在耐药肿瘤细胞中维持 DOX 浓度在最佳水平；（2）小的纳米结构 DOX 通过尺寸依赖性的核转运有效地进入细胞核，从而增强治疗效果；（3）通过减少循环过程中的 DOX 泄漏，改善了药代动力学和生物分布。
本研究中开发的系统有可能为耐药肿瘤提供新的治疗方法。
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