A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy.
A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy.
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DOI：
10.1016/j.phrs.2011.06.015
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发表时间：
2011-10
影响因子：
9.3
通讯作者：
Zheyu Shen;Wei Wei-Wei;Hideyuki Tanaka;K. Kohama;G. Ma;T. Dobashi;Y. Maki;Hong-Hui Wang;J. Bi;S. Dai
中科院分区：
文献类型：
--
作者：
Zheyu Shen;Wei Wei-Wei;Hideyuki Tanaka;K. Kohama;G. Ma;T. Dobashi;Y. Maki;Hong-Hui Wang;J. Bi;S. Dai
为了减少肿瘤化疗的毒副作用，开发了一种新型的半乳糖胺介导的药物载体-半乳糖胺偶联白蛋白纳米粒（GAL-AN），用于肝癌的靶向治疗。以戊二醛为交联剂，采用去溶剂化法制备了白蛋白纳米粒（AN）和阿霉素纳米粒（DOX-AN）。形貌研究表明，合成的纳米粒子为球形结构，平均粒径约为200 nm。通过碳二亚胺化学法将半乳糖胺功能配体（GAL）引入到AN和DOX-AN表面，得到GAL-AN和GAL-DOX-AN。细胞摄取和动力学研究表明，由于HepG 2细胞表面存在脱唾液酸糖蛋白受体，GAL-AN能够选择性地掺入HepG 2细胞而不是AoSMC细胞。MTT法检测AN和GAL-AN对HepG 2细胞的杀伤作用，结果表明：AN和GAL-AN对HepG 2细胞均无毒性，GAL-DOX-AN对HepG 2细胞的杀伤作用优于DOX-AN。因此，我们的研究结果表明，GAL-AN和GAL-DOX-AN通过识别GAL和去唾液酸糖蛋白受体与HepG 2细胞具有特异性相互作用，这使得GAL-AN成为一种有希望的肝癌治疗抗癌药物递送载体。
In order to minimize the side effect of cancer chemotherapy, a novel galactosamine-mediated drug delivery carrier, galactosamine-conjugated albumin nanoparticles (GAL-AN), was developed for targeted liver cancer therapy. The albumin nanoparticles (AN) and doxorubicin-loaded AN (DOX-AN) were prepared by the desolvation of albumin in the presence of glutaraldehyde crosslinker. Morphological study indicated the spherical structure of these synthesized particles with an average diameter of around 200nm. The functional ligand of galactosamine (GAL) was introduced onto the surfaces of AN and DOX-AN via carbodiimide chemistry to obtain GAL-AN and GAL-DOX-AN. Cellular uptake and kinetic studies showed that GAL-AN is able to be selectively incorporated into the HepG2 cells rather than AoSMC cells due to the existence of asialoglycoprotein receptors on HepG2 cell surface. The cytotoxicity, measured by MTT test, indicated that AN and GAL-AN are non-toxic and GAL-DOX-AN is more effective in HepG2 cell killing than that of DOX-AN. As such, our results implied that GAL-AN and GAL-DOX-AN have specific interaction with HepG2 cells via the recognition of GAL and asialoglycoprotein receptor, which renders GAL-AN a promising anticancer drug delivery carrier for liver cancer therapy.