Targeting of glut5 for transporter-mediated drug-delivery is contingent upon substrate hydrophilicity

Authors

Nazanin Nahrjou, Michigan Technological University
Avik Ghosh, Michigan Technological UniversityFollow
Marina Tanasova, Michigan Technological UniversityFollow

Document Type

Article

Publication Date

5-11-2021

Department

Department of Chemistry

Abstract

Specific link between high fructose uptake and cancer development and progression highlighted fructose transporters as potential means to achieve GLUT-mediated discrimination between normal and cancer cells. The gained expression of fructose-specific transporter GLUT5 in various cancers offers a possibility for developing cancer-specific imaging and bioactive agents. Herein, we explore the feasibility of delivering a bioactive agent through cancer-relevant fructose-specific transporter GLUT5. We employed specific targeting of GLUT5 by 2,5-anhydro-D-mannitol and investigated several drug conjugates for their ability to induce cancer-specific cytotoxicity. The proof-of-concept analysis was carried out for conjugates of chlorambucil (CLB) in GLUT5-positive breast cancer cells and normal breast cells. The cytotoxicity of conjugates was assessed over 24 h and 48 h, and significant dependence between cancer-selectivity and conjugate size was observed. The differences were found to relate to the loss of GLUT5-mediated uptake upon increased conjugate size and hydrophobicity. The findings provide information on the substrate tolerance of GLUT5 and highlight the importance of maintaining appropriate hydrophilicity for GLUT-mediated delivery.

Publisher's Statement

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Publisher’s version of record: https://doi.org/10.3390/ijms22105073

Publication Title

International Journal of Molecular Sciences

Recommended Citation

Nahrjou, N., Ghosh, A., & Tanasova, M. (2021). Targeting of glut5 for transporter-mediated drug-delivery is contingent upon substrate hydrophilicity. International Journal of Molecular Sciences, 22(10). http://doi.org/10.3390/ijms22105073
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/14869

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

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Publisher's PDF