Glucose-installed biodegradable polymeric micelles for cancer-targeted drug delivery system: synthesis, characterization and in vitro evaluation
- 165 Downloads
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. 18FGD-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(ε-caprolactone) (PEG-b-PCL) was synthesized where terminal group of the PEG chain was installed with glucose molecules. The 1H-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 22 nm 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.
This research project was supported by Mahidol University. Man Theerasilp was partially supported by the Center for Innovation in Chemistry (PERCH-CIC), Commission on Higher Education, Ministry of Education is gratefully acknowledged.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Yu J-M, Li W-D, Lu L, Zhou X-Y, Wang D-Y, Li H-M, et al. Preparation and characterization of galactosylated glycol chitosan micelles and its potential use for hepatoma-targeting delivery of doxorubicin. J Mater Sci. 2014;25:691–701.Google Scholar
- 14.Nittayacharn P, Nasongkla N. Development of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy. J Mater Sci. 2017;28:101.Google Scholar
- 15.Eawsakul K, Chinavinijkul P, Saeeng R, Chairoungdua A, Tuchinda P, Nasongkla N. Preparation and characterizations of RSPP050-loaded polymeric micelles using poly(ethylene glycol)-b-poly(ε-caprolactone) and poly(ethylene glycol)-b-poly(D,L-lactide). Chem Pharm Bull. 2017;65:530–7.CrossRefGoogle Scholar
- 16.Tambunlertchai S, Srisang S, Nasongkla N. Development of antimicrobial coating by later-by-layer dip coating of chlorhexidine-loaded micelles. J Mater Sci. 2017;28:90.Google Scholar
- 18.Puntawee S, Theerasilp M, Reabroi S, Saeeng R, Piyachaturawat P, Chairoungdua A, et al. Solubility enhancement and in vitro evaluation of PEG- b -PLA micelles as nanocarrier of semi-synthetic andrographolide analogue for cholangiocarcinoma chemotherapy. Pharm Dev Technol. 2016;21:437–44.Google Scholar
- 32.Liu M, Huang G, Cong Y, Tong G, Lin Z, Yin Y. et al. The preparation and characterization of micelles from poly(y-glutamic acid)-graft-poly(l-lactide) and the cellular uptake thereof. J Mater Sci. 2015;26:187.Google Scholar
- 33.Wenger RH, Camenisch G, Desbaillets I, Chilov D, Gassmann M. Up-regulation of hypoxia-inducible factor-1α is not sufficient for hypoxic/anoxic p53 induction. Cancer Res. 1998;58:5678–80.Google Scholar
- 36.Effert P, Beniers AJ, Tamimi Y, Handt S, Jakse G. Expression of glucose transporter 1 (Glut-1) in cell lines and clinical specimens from human prostate adenocarcinoma. Anticancer Res. 2004;24(5A):3057–64.Google Scholar