可共载基因与敏化剂用以增强多西他赛抗肿瘤效果的脂质纳米载药系统的制备与评价

doi:10.5246/jcps.2014.03.018

中国药学(英文版)

可共载基因与敏化剂用以增强多西他赛抗肿瘤效果的脂质纳米载药系统的制备与评价

孟婷婷, 李井泉, 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:2014-02-18 修回日期:2014-02-25 出版日期:2014-03-13 发布日期:2014-03-10
通讯作者: *Corresponding author. Tel.:13910584494; E-mail: qixr@bjmu.edu.cn
作者简介:*Corresponding author. Tel.:13910584494; E-mail: qixr@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81273454), Beijing Natural Science Foundation (Grant No. 7132113), and Doctoral Foundation of the Ministry of Education (Grant No. 20100001110056 and 20130001110055).

Preparation and evaluation of lipid-matrix nanocarrier co-delivery gene and sensibilizer to elevate docetaxel antitumor

Tingting Meng, Jingquan Li, Xianrong Qi^*

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

Received:2014-02-18 Revised:2014-02-25 Online:2014-03-13 Published:2014-03-10
Contact: *Corresponding author. Tel.:13910584494; E-mail: qixr@bjmu.edu.cn
About author:*Corresponding author. Tel.:13910584494; E-mail: qixr@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81273454), Beijing Natural Science Foundation (Grant No. 7132113), and Doctoral Foundation of the Ministry of Education (Grant No. 20100001110056 and 20130001110055).

摘要/Abstract

摘要：

本研究制备了一种纳米载药系统, 通过对几种化学或基因药物的同时递送, 实现多种药物的协同效应或降低肿瘤对药物的耐药性, 从而达到提高肿瘤治疗的目的。在本研究中, 通过考察粒径分布及载药量对不同的阳性脂材进行筛选, 成功制备可以同时传递阴离子小干扰RNA (siRNA)和化疗药物多西他赛的阳性纳米脂质载体 (cNLC)。同时, 利用能与肝癌细胞表面特异性结合的新型肽SP94对cNLC的表面进行修饰, 最终制得具有主动靶向功能的cNLC。琼脂糖凝胶色谱结果显示制得的cNLC可以有效的装载siRNA。超滤离心法去除游离药物后, HPLC图谱显示cNLC能够高效的包载多西他赛。与市售制剂泰索帝相比, 制得的SP94-cNLC显示出更强的细胞毒性, 这表明SP94修饰的cNLC能更高效的递送多西他赛进入肝癌细胞。而在姜黄素和多西他赛共载的NLC中, 通过姜黄素对多西他赛的敏化作用提高多西他赛在侵袭性癌细胞中的细胞毒性, 这种共载系统能够改善化疗药物单独使用时疗效较差的缺点。

关键词: 共传递系统, 多西他赛, 小干扰RNA, 姜黄素, 制剂

Abstract:

It is a promising treatment strategy to use a nanoparticle-based drug delivery system for cancer patients, which can simultaneously deliver multiple drugs or genes in combination with therapy to induce synergistic effects and suppress drug resistanceto the tumor. In this study, cationic nanostructured lipid carriers (cNLC) for co-loading anionic small-interfering RNAs (siRNA) and chemotherapeutic docetaxel (DTX) were prepared from different cationic lipids based on particle distribution and loading efficiency. In order to increase the cNLC's positive targeting capacity, a novel peptide SP94 was bound to the surface of cNLC (SP94-cNLC). The cNLC showed good efficiency in loading siRNA and DTX. The SP94-cNLC revealed a better cytotoxicity compared with cNLC and Taxotere^®, indicating that SP94 could successfully enhance the internalization capacity of nanoparticles to the liver cancer cells. This new type of cNLC is a potential vehicle when using in co-delivery of chemotherapeuticsand siRNAs. The curcumin (CUR)/DTX co-delivery NLC could load both CUR and DTX in high efficiency and showed a sensibilization to DTX chemotherapy. The sensibilization was more obvious when it was used in the aggressive and resistant cancer cells. This CUR/DTX co-delivery system had good potential in treating cancer cells when chemotherapy drug showed little effect alone.

Key words: Co-delivery system, Docetaxel, Small-interfering RNAs, Curcumin, Preparation

中图分类号:

R994

Supporting:

National Natural Science Foundation of China (Grant No. 81273454), Beijing Natural Science Foundation (Grant No. 7132113), and Doctoral Foundation of the Ministry of Education (Grant No. 20100001110056 and 20130001110055).

孟婷婷, 李井泉, 齐宪荣. 可共载基因与敏化剂用以增强多西他赛抗肿瘤效果的脂质纳米载药系统的制备与评价[J]. 中国药学(英文版), DOI: 10.5246/jcps.2014.03.018.

Tingting Meng, Jingquan Li, Xianrong Qi. Preparation and evaluation of lipid-matrix nanocarrier co-delivery gene and sensibilizer to elevate docetaxel antitumor[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.03.018.

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可共载基因与敏化剂用以增强多西他赛抗肿瘤效果的脂质纳米载药系统的制备与评价

Preparation and evaluation of lipid-matrix nanocarrier co-delivery gene and sensibilizer to elevate docetaxel antitumor

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