Glucose-installed biodegradable polymeric micelles for cancer-targeted drug delivery system: synthesis, characterization and in vitro evaluation

摘要

Glucose metabolism of cancer can be used as a strategy to target cancer cells which exhibit altered glycolytic rate. The facilitated glucose transporter (Glut) plays an important role in enhancement glycolytic rate resulting in increased glucose uptake into cancer cells. (18)FGD-PET image is an example for using Glut as a targeting to diagnose the high glycolytic rate of tumor. Thus, Glut may be adapted to target cancer cells for drug delivery system. Herein, biodegradation polymeric micelles target cancer cells by Glut was fabricated. The amphiphilic block copolymer of poly(ethylene glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL) was synthesized where terminal group of the PEG chain was installed with glucose molecules. The H-1-NMR confirmed the existence of glucose moiety from two distinct peaks (5.2 and 4.7 ppm) of protons at anomeric carbon of glucose. Glucose-PEG-b-PCL spontaneously forms micelles in an aqueous solution. The size and zeta potential were 22nm and -7 mv, respectively. Glucose-micelles have high stability, and no evidence of cytotoxicity was found after incubation for 7 days. Doxorubicin, used as a fluorescent probe, was loaded into glucose-micelles. The enhanced amount of doxorubicin as a result of glucose-micelles in PC-3, MCF-7 and HepG2 was evaluated by fluorescence microscopy and flow cytometer. Glucose molecules on the surface of micelles increased internalization and enhanced uptake of micelles via bypassing endocytosis pathway. These results show the use of glucose as a targeting ligand on the micelle surface to target cancer cells via Glut.[GRAPHICS]