Synergistically Enhanced Therapeutic Effect of a Carrier-Free HCPT/DOX Nanodrug on Breast Cancer Cells through Improved Cellular Drug Accumulation
Synergistically Enhanced Therapeutic Effect of a Carrier-Free HCPT/DOX Nanodrug on Breast Cancer Cells through Improved Cellular Drug Accumulation
复制标题
无载体 HCPT/DOX 纳米药物通过改善细胞药物积累协同增强对乳腺癌细胞的治疗效果
DOI：
10.1021/mp500744m
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发表时间：
2015-07-01
影响因子：
4.9
通讯作者：
Liang, Xing-Jie
中科院分区：
文献类型：
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作者：
Chen, Fei;Zhao, Yuanyuan;Liang, Xing-Jie
我们有兴趣开发两种或两种以上化疗药物同时输送的系统。简单的药物物理混合可能会降低治疗效果，并产生意想不到的甚至危险的副作用。例如，当10-羟基喜树碱(HCPT)和阿霉素(DOX)注射溶液混合时，在临床实践中疗效实际上是降低的。在这项研究中，我们证明了当羟基喜树碱和多柔比星结合成单个纳米颗粒时，它们在体外对肿瘤细胞的毒性被协同增强。我们使用了一种简单、绿色的再沉淀方法，通过药物分子的自纳米结晶，成功地创建了一种无载体的双药给药系统。当羟基喜树碱和DOX共组装时，它们形成了表面带正电荷的小的球形纳米地毯颗粒。与单独使用羟基喜树碱相比，细胞对羟基喜树碱的摄取得到改善，核聚集量增加了1.57倍。无载体的羟基喜树碱/多柔比星纳米粒在体外对乳腺癌细胞表现出增强的协同杀伤作用，而当羟基喜树碱与多柔比星在高浓度时直接混合时，则表现出拮抗作用。
We are interested in developing systems for simultaneous delivery of two or more chemotherapeutic agents. Simple physical mixing of drugs may reduce the therapeutic effect and cause unexpected or even dangerous side-effects. For example, when 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) injection solutions are mixed, the curative effect is actually reduced in clinical practice. In this study we demonstrated that when HCPT and DOX are combined into a single nanoparticle, their toxicity to tumor cells in vitro is synergistically enhanced. We used a simple and "green" reprecipitation method to successfully create a carrier-free dual-drug delivery system by self-nanocrystallization of the drug molecules. When HCPT and DOX were coassembled, they formed small, spherical nanodrug particles with a positive surface charge. Cellular uptake of HCPT was improved and nuclear accumulation increased as much as 1.57-fold in comparison to HCPT alone. The carrier-free HCPT/DOX nanoparticles demonstrated enhanced synergistic cytotoxicity against breast cancer cells in vitro, while an antagonistic effect was observed when HCPT and DOX were directly mixed at high concentration.