制备并表征叶酸-聚乙二醇-接枝-三甲基壳聚糖，通过叶酸受体介导的内吞作用实现蛋白质的细胞内运输。

Preparation and characterization of folate-poly(ethylene glycol)-grafted-trimethylchitosan for intracellular transport of protein through folate receptor-mediated endocytosis.

机构信息

Sichuan University, Chengdu, China.

出版信息

J Biotechnol. 2010 Jan 1;145(1):47-53. doi: 10.1016/j.jbiotec.2009.09.007.

DOI:10.1016/j.jbiotec.2009.09.007

PMID:19770010

Abstract

To develop a receptor-mediated intracellular delivery system that can transport therapeutic proteins to specific tumor cells, folate-poly(ethylene glycol)-grafted-trimethylchitosan (folate-PEG-g-TMC) was synthesized. Nano-scaled spherical polyelectrolyte complexes between the folate-PEG-g-TMC and fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) were prepared under suitable weight ratio of copolymer to FITC-BSA by ionic interaction between the positively charged copolymers and the negatively charged FITC-BSA. Intracellular uptake of FITC-BSA was specifically enhanced in SKOV3 cells (folate receptor over-expressing cell line) through folate receptor-mediated endocytosis compared with A549 cells (folate receptor deficient cell line). Folate-PEG-g-TMC shows promise for intracellular transport of negatively charged therapeutic proteins into folate receptor over-expressing tumor cells.

摘要

为了开发一种能够将治疗性蛋白质递送到特定肿瘤细胞的受体介导的细胞内递药系统，合成了叶酸-聚乙二醇-接枝-三甲基壳聚糖（folate-PEG-g-TMC）。在合适的共聚物与 FITC-BSA 的重量比下，通过正电荷共聚物与负电荷 FITC-BSA 之间的离子相互作用，制备了 folate-PEG-g-TMC 与异硫氰酸荧光素标记牛血清白蛋白（FITC-BSA）之间的纳米级球形聚电解质复合物。与 A549 细胞（叶酸受体缺陷细胞系）相比，通过叶酸受体介导的内吞作用，SKOV3 细胞（叶酸受体过表达细胞系）中 FITC-BSA 的细胞内摄取特异性增强。Folate-PEG-g-TMC 有望将带负电荷的治疗性蛋白质递送到叶酸受体过表达的肿瘤细胞内。