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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Mahidol University, Puttamonthon, Nakorn Pathom, 73170, Thailand

    Man Theerasilp, Punlop Chalermpanapun & Norased Nasongkla

  2. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Mahidol University, Bangkok, 10400, Thailand

    Man Theerasilp & Norased Nasongkla

  3. Department of Chemistry, Mahidol University, Nakorn patom, 73170, Thailand

    Panya Sunintaboon

  4. Department of Radiology, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand

    Witaya Sungkarat

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  1. Man Theerasilp
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Correspondence to Norased Nasongkla.

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Theerasilp, M., Chalermpanapun, P., Sunintaboon, P. et al. Glucose-installed biodegradable polymeric micelles for cancer-targeted drug delivery system: synthesis, characterization and in vitro evaluation. J Mater Sci: Mater Med 29, 177 (2018). https://doi.org/10.1007/s10856-018-6177-7

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