Galactosylated nanocrystallites of insoluble anticancer drug for liver-targeting therapy: an in vitro evaluation
Galactosylated nanocrystallites of insoluble anticancer drug for liver-targeting therapy: an in vitro evaluation
复制标题
用于肝脏靶向治疗的不溶性抗癌药物半乳糖基化纳米晶体：体外评估
DOI：
10.2217/nnm.10.27
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发表时间：
2010-06-01
期刊：
影响因子：
5.5
通讯作者：
Ma, Guang-Hui
中科院分区：
文献类型：
--
作者：
Wei, Wei;Yue, Zhan-Guo;Ma, Guang-Hui
目的：低水溶性已成为许多抗癌药物的固有特性，这对从实验室到临床的转化构成了障碍。本研究采用一种简便的方法制备了10-羟基喜树碱（HCPT）纳米微粒，并验证了其用于肝靶向治疗的可行性。材料与方法：利用半乳糖化壳聚糖的软模板作用制备羟基喜树碱纳米粒子。通过将这些纳米颗粒暴露于人肝细胞癌HepG 2细胞来评价内化概况、细胞内运输、药物活性和细胞活力。结果如下：半乳糖基化壳聚糖位于HCPT纳米晶体上，不仅稳定了水介质中的制剂，而且通过脱唾液酸糖蛋白受体介导的途径增强了细胞内化。这些纳米材料还表现出核进入和主动HCPT递送的优点，因此可以实现更好的抗癌细胞毒性。结论：半乳糖基化羟基喜树碱纳米粒具有良好的肝靶向治疗上级特性。
Aim: Low solubility in water has become an intrinsic property of many anticancer drugs, which poses a hurdle in the translation from the bench to the clinic. In this study, we developed a facile method to prepare 10-hydroxycamptothecin (HCPT) nanocrystallites and testified their feasibility for liver-targeting therapy. Materials & methods: HCPT nanocrystallites were prepared under the soft template effect of galactosylated chitosan. The internalization profile, intracellular trafficking, drug activity and cell viability were evaluated by exposing these nanocrystallites to human hepatocellular carcinoma HepG2 cells. Results: Galactosylated chitosan located on the HCPT nanocrystallites not only stabilized the formulation in aqueous medium, but also enhanced the cellular internalization through an asialoglycoprotein receptor-mediated pathway. These nanocrystallites also exhibited the advantages of nuclear entry and active HCPT delivery, and consequently better anticancer cytotoxicity could be achieved. Conclusion: These data strongly support the superior properties of galactosylated HCPT nanocrystallites on liver-targeting therapy.