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Article

Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity

1
Chemistry Department, Michigan Technological University, Houghton, MI 49931, USA
2
Health Research Institute, Michigan Technological University, Houghton, MI 49931, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Valentina De Falco
Int. J. Mol. Sci. 2021, 22(10), 5073; https://doi.org/10.3390/ijms22105073
Received: 7 April 2021 / Revised: 28 April 2021 / Accepted: 8 May 2021 / Published: 11 May 2021
(This article belongs to the Special Issue Targeted Cancer Therapy and Mechanisms of Resistance 2.0)
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. View Full-Text
Keywords: sugar transport; fructose transport; GLUT5; drug conjugates; targeted delivery; cancer selectivity sugar transport; fructose transport; GLUT5; drug conjugates; targeted delivery; cancer selectivity
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MDPI and ACS Style

Nahrjou, N.; Ghosh, A.; Tanasova, M. Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity. Int. J. Mol. Sci. 2021, 22, 5073. https://doi.org/10.3390/ijms22105073

AMA Style

Nahrjou N, Ghosh A, Tanasova M. Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity. International Journal of Molecular Sciences. 2021; 22(10):5073. https://doi.org/10.3390/ijms22105073

Chicago/Turabian Style

Nahrjou, Nazanin, Avik Ghosh, and Marina Tanasova. 2021. "Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity" International Journal of Molecular Sciences 22, no. 10: 5073. https://doi.org/10.3390/ijms22105073

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