College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
Biomaterials. 2011 Dec;32(35):9515-24. doi: 10.1016/j.biomaterials.2011.08.074. Epub 2011 Sep 9.
The effective passage of drug formulations into tumor cells is a key factor in the development of nanoscale delivery systems. However, rapid cellular uptake with reduced toxicity remains a great challenge for efficient and safe delivery. In this study, we first use gemini quaternary ammonium (GQA) as a cell internalization promoter to enhance the cellular uptake of drug nanocarriers. It is found that a twenty times faster cell internalization could be achieved by introducing GQA into biodegradable multiblock polyurethane nanomicelles, as confirmed by flow cytometry and confocal laser scanning microscopy (CLSM) studies. Meanwhile, an added methoxyl-poly(ethylene glycol) (mPEG) outer corona could protect these cationic micelles from cytotoxicity at high concentrations, as verified by methyl tetrazolium (MTT) assay. Moreover, GQA not only acts as an enhancer for rapid cellular entry, but also plays an important role in controlled self-assembly and high drug loading capacity. Our work offers a new understanding on the role of cationic surfactants; and provides a facile and economical approach for the design of versatile drug nanocarriers to achieve efficient delivery and good biocompatibility.
药物制剂有效进入肿瘤细胞是纳米递药系统发展的关键因素。然而，如何实现高效、低毒的快速细胞内化仍然是一个巨大的挑战。在本研究中，我们首先使用双子季铵盐（GQA）作为细胞内化促进剂来增强药物纳米载体的细胞摄取。通过将 GQA 引入可生物降解的多嵌段聚氨酯纳米胶束中，发现细胞内化速度提高了二十倍，这一点通过流式细胞术和共聚焦激光扫描显微镜（CLSM）研究得到了证实。同时，添加甲氧基聚乙二醇（mPEG）外层冠可以保护这些阳离子胶束免受高浓度时的细胞毒性，这一点通过甲基噻唑基四唑（MTT）测定得到了验证。此外，GQA 不仅可以作为快速细胞进入的增强剂，而且在控制自组装和高载药量方面也起着重要作用。我们的工作为阳离子表面活性剂的作用提供了新的认识，并为设计多功能药物纳米载体以实现高效传递和良好生物相容性提供了一种简便、经济的方法。
