Huang Can, Li Na-Mei, Gao Pei, Yang Sa, Ning Qian, Huang Wen, Li Zhi-Ping, Ye Peng-Ju, Xiang Li, He Dong-Xiu, Tan Xiang-Wen, Yu Cui-Yun
a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
b Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy & Pharmacology University of South China , Hengyang , China , and.
Drug Deliv. 2017 Nov;24(1):459-466. doi: 10.1080/10717544.2016.1264499.
A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.
本研究报道了一种新型的大分子前药递送系统。对基于N-半乳糖基化壳聚糖-5-氟尿嘧啶乙酸共轭物（GC-FUA）的纳米颗粒递送系统进行了体外和体内评估。通过体外牛血清白蛋白吸附试验和溶血活性检测筛选了GC-FUA-NPs的生物相容性。在HepG2和A549细胞中的细胞毒性和细胞摄取研究表明，与游离5-Fu相比，GC-FUA-NPs通过细胞表面过表达的去唾液酸糖蛋白受体（ASGPR）介导的细胞内吞作用，在杀死癌细胞方面发挥了很大作用。药代动力学研究进一步表明，在Sprague-Dawley（SD）大鼠的血液循环中，载药纳米颗粒的半衰期比游离5-Fu长得多。在昆明小鼠中研究了组织分布，结果表明GC-FUA-NPs具有长循环效应。获得的数据表明，GC-FUA-NP是一种非常有前景的用于高效治疗肝细胞癌的药物递送系统。
