肝癌靶向的阳离子脂质体共递送多西他赛和siRNA的研究

doi:10.5246/jcps.2014.10.085

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (10): 667-673.DOI: 10.5246/jcps.2014.10.085

肝癌靶向的阳离子脂质体共递送多西他赛和siRNA的研究

李井泉, 仰浈臻, 孟婷婷, 齐宪荣^*

北京大学医学部天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2014-05-08 修回日期:2014-05-30 出版日期:2014-10-31 发布日期:2014-06-09
通讯作者: Tel.: 86-10-82801584
基金资助:
National Natural Science Foundation of China (Grant No. 81273454), Beijing National Science Foundation (Grant No. 7132113), Doctoral Foundation of the Ministry of Education (Grant No. 20130001110055) and Innovation Team of Ministry of Education (Grant No. BMU20110263).

The use of cationic liposomes to co-deliver docetaxel and siRNA for targeted therapy of hepatocellular carcinoma

Jingquan Li, Zhenzhen Yang, Tingting Meng, Xianrong Qi^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Sciences Center, Beijing 100191, China

Received:2014-05-08 Revised:2014-05-30 Online:2014-10-31 Published:2014-06-09
Contact: Tel.: 86-10-82801584
Supported by:
National Natural Science Foundation of China (Grant No. 81273454), Beijing National Science Foundation (Grant No. 7132113), Doctoral Foundation of the Ministry of Education (Grant No. 20130001110055) and Innovation Team of Ministry of Education (Grant No. BMU20110263).

摘要/Abstract

摘要：

肝细胞癌是全世界最常见的恶性肿瘤之一, 居癌症相关死亡原因第三位。通过在纳米载体系统上修饰靶向配体可将药物主动靶向至肿瘤细胞。随着药物制剂学的发展, 采用纳米给药系统共递送化疗药物与基因药物成为了治疗肿瘤的一种手段。本研究通过薄膜超声法制备了共包载多西他赛(DTX)和小干扰RNA(siRNA)的脂质体, 并用SP94对其进行修饰。血清稳定性试验表明, 脂质体能较好地保护siRNA免受血清中核酸酶的降解。与未修饰的阳离子脂质体相比, SP94修饰的阳离子脂质体显著增强了制剂的在肿瘤细胞内的摄取和对肿瘤细胞的抗增殖作用, 表明了SP94的主动靶向作用。本课题成功构建了主动靶向肝癌的共包载DTX和siRNA的阳离子纳米粒给药系统, 为肝细胞癌的治疗提供了新的研究思路。

关键词: SP94, 肝癌, 脂质体, 多西他赛, 小干扰RNA

Abstract:

Hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel (DTX) and small interfering RNA (siRNA). The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.

Key words: SP94, Hepatocellular carcinoma, Liposomes, Docetaxel, siRNA

中图分类号:

R943

Supporting:

李井泉, 仰浈臻, 孟婷婷, 齐宪荣. 肝癌靶向的阳离子脂质体共递送多西他赛和siRNA的研究[J]. 中国药学(英文版), 2014, 23(10): 667-673.

Jingquan Li, Zhenzhen Yang, Tingting Meng, Xianrong Qi . The use of cationic liposomes to co-deliver docetaxel and siRNA for targeted therapy of hepatocellular carcinoma[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(10): 667-673.

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肝癌靶向的阳离子脂质体共递送多西他赛和siRNA的研究

The use of cationic liposomes to co-deliver docetaxel and siRNA for targeted therapy of hepatocellular carcinoma

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