Ovarian cancer targeted hyaluronic acid-based nanoparticle system for paclitaxel delivery to overcome drug resistance
Ovarian cancer targeted hyaluronic acid-based nanoparticle system for paclitaxel delivery to overcome drug resistance
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DOI：
10.3109/10717544.2015.1101792
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发表时间：
2016-06
期刊：
影响因子：
6
通讯作者：
Liping Wang;Erxia Jia
中科院分区：
文献类型：
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作者：
Liping Wang;Erxia Jia
摘要目的：大多数原发性人类卵巢肿瘤和腹膜植入物以及肿瘤血管内皮细胞表达CD 44家族的细胞表面蛋白聚糖，其天然配体是透明质酸（HA）。紫杉醇（PTX）是一种有效的化疗药物，广泛用于治疗多种癌症，包括卵巢癌。本研究旨在开发一种基于HA的载PTX纳米粒系统，以提高卵巢癌的治疗效果。方法：制备载PTX阳离子纳米脂质纳米粒（PTX NLC）。然后通过静电吸附将HA-PE涂覆到PTX-NLC上以形成HA-PTX-NLC。在SKOV 3人卵巢癌细胞（SKOV 3细胞）和PTX抗性SKOV 3细胞（SKOV 3/PTX细胞）上分析体外肿瘤细胞抑制效率。用携带SKOV 3卵巢癌细胞异种移植物的小鼠评价体内抗癌能力。结果：HA-PTX-NLC的平均粒径为163 nm，PTX的掺入率大于80%。HA-PTX-NLCs对SKOV 3细胞和SKOV 3/PTX细胞的体外存活率有明显的抑制作用。在卵巢癌细胞模型中，观察到肿瘤生长的显著减少，而常规PTX注射组没有达到显著性。结论：该研究表明，新构建的HA-PTX-NLC在体外和体内治疗功效方面获得了显著改善的结果。这些发现强烈支持基于HA的纳米系统用于PTX递送的优越性，从而增强卵巢癌化疗的功效。
Abstract Objective: Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid (HA). Paclitaxel (PTX) is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including ovarian cancer. This study aimed to develop a HA-based PTX-loaded nanoparticle system to improve the ovarian cancer therapeutic effects. Methods: PTX-loaded cationic nanostructured lipid nanoparticles (PTX-NLCs) were prepared. HA-PE was then coated onto the PTX-NLCs by electrostatic adsorption to form HA-PTX-NLCs. In vitro tumor cell inhibition efficiency was analyzed on SKOV3 human ovarian cancer cells (SKOV3 cells) and PTX-resistant SKOV3 cells (SKOV3/PTX cells). In vivo anticancer ability was evaluated with mice bearing SKOV3 ovarian cancer cells xenografts. Results: HA-PTX-NLCs had an average diameter of 163 nm, and PTX was incorporated with an efficiency of over 80%. The in vitro viability of SKOV3 cells and SKOV3/PTX cells was obviously inhibited by HA-PTX-NLCs. In the ovarian cancer cells model, significant reduction in tumor growth was observed, whereas the conventional PTX injection group did not achieve significance. Conclusion: This study demonstrated that significantly improved results were obtained by the newly constructed HA-PTX-NLCs, in terms of in vitro and in vivo therapeutic efficacy. These findings strongly support the superiority of HA based nano-system for the PTX delivery, thus enhance the efficacy of ovarian cancer chemotherapy.