同源细胞膜包覆智能释药纳米粒用于肝癌靶向治疗

doi:10.11944/j.issn.1000-0518.2020.01.190121

摘要/Abstract

摘要：

近年来,纳米药物递送系统在癌症治疗方面的应用受到广泛关注。传统的纳米药物递送系统存在生物相容性差、靶向性缺乏、在肿瘤部位释药缓慢等问题。本文设计制备了一种同源细胞膜(M)包覆、癌细胞还原微环境控制释药的脂质体纳米粒子(命名为P-ss-G/D/Sf@M)来递送肝癌治疗药物索拉非尼(Sf)用于肝癌的靶向治疗。利用薄膜水化法结合静电吸附及过膜挤压法制备包覆细胞膜的空白(P-ss-G/D@M)及载药(P-ss-G/D/Sf@M)纳米粒子。 P-ss-G/D/Sf@M对Sf的载药量为7.2%,包封率为79.9%。体外释药结果显示,P-ss-G/D/Sf@M在还原条件下会加快药物的释放,48 h时药物释放量达到65%以上,较非还原条件下释药量提高了25%。体外细胞实验结果证明,包覆肝癌细胞膜的纳米粒子更易被肝癌细胞摄取,表现了对肝癌细胞的靶向性,同时在肿瘤细胞高浓度谷胱甘肽(GSH)还原环境作用下,纳米粒子中的二硫键断裂,迅速释放药物,与非还原敏感载药纳米粒子相比,显著抑制肝癌细胞生长,提高细胞凋亡率。因此,本文制备的同源细胞膜包覆的智能释药载体有可能用于今后的癌症治疗中。

关键词: 细胞膜靶向, 谷胱甘肽响应, 脂质体, 聚乳酸-羟基乙酸, 索拉非尼

Abstract:

Nanoparticle drug delivery system has played an important role in enhancing the efficacy of traditional chemotherapy drugs in recent years. However, the main challenges faced by conventional nanoparticle include poor biocompatibility, low specific targeting and slow drug release in target sites. In this work, we fabricated an efficient hepatocellular carcinoma-targeting liposome system functionalized with a redox-cleavable and homologous cell membrane(M)-targeting. The blank (P-ss-G/D@M) and drug-loaded (P-ss-G/D/Sf@M) nanoparticles coated with cell membrane were prepared by thin-film hydration method combined with electrostatic adsorption and membrane extrusion. The drug-loading amount of sorafenib was 7.2%, and the encapsulation efficiency was 79.9%. The results of in vitro drug release showed that P-ss-G/D/Sf@M accelerated drug release under reducing conditions, and the drug release rate was more than 65% at 48 hours, which was 25% higher than that under non-reducing conditions. In vitro study demonstrated that nanoparticles coated with hepatoma cell membrane were more easily taken into hepatoma cells, showing the targeting of hepatocellular carcinoma. At the same time, the disulfide bonds in the nanoparticles broke and drugs were rapidly released under the high concentration of glutathione (GSH) in the tumor cells. Compared with non-reducing sensitive drug-loaded nanoparticles, P-ss-G/D/Sf@M could significantly inhibit the growth of hepatoma cells (Hep-G2) and increase the apoptosis rate of hepatoma cells. Therefore, the homologous cell membrane-coated smart drug delivery carrier prepared herein is likely to be used to treat hepatocellular carcinoma in future.

Key words: cell membrane targeting, glutathione-response, liposomes, poly(lactic-co-glycolic acid), sorafenib

夏颖, 夏菁, 崔洪燕, 钱明, 张留伟, 陈麒先, 王静云. 同源细胞膜包覆智能释药纳米粒用于肝癌靶向治疗[J]. 应用化学, 2020, 37(1): 69-79.

XIA Ying, XIA Jing, CUI Hongyan, QIAN Ming, ZHANG Liuwei, CHEN Qixian, WANG Jingyun. Homologous Cell Membrane Coated Smart Drug-Release Nanoparticles for Targeted Hepatocellular Carcinoma Therapy[J]. Chinese Journal of Applied Chemistry, 2020, 37(1): 69-79.

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