Menue

Publications

Authors Sztandera, K. ; Dzialak, P. ; Marcinkowska, M. ; Stanczyk, M. ; Gorzkiewicz, M. ; Janaszewska, A. ; Klajnert-Maculewicz, B.
Title Sugar modification enhances cytotoxic activity of PAMAM-doxorubicin conjugate in glucose-deprived MCF-7 cells - possible role of GLUT1 transporter
Date 21.08.2019
Number 57022
Abstract Purpose: In order to overcome the obstacles and side effects of classical chemotherapy, numerous studies have been performed to develop the treatment based on targeted transport of active compounds directly to the site of action. Since tumor cells are featured with intensified glucose metabolism, we set out to develop innovative, glucose-modified PAMAM dendrimer for the delivery of doxorubicin to breast cancer cells. Methods: PAMAM-dox-glc conjugate was synthesized and characterized by 1H NMR, FT-IR, size and zeta potential measurements. The drug release rate from conjugate was evaluated by dialysis under different pH conditions. The expression level of GLUT family receptors in cells cultured in full and glucose-deprived medium was evaluated by quantitative real-time RT-PCR and flow cytometry. The cytotoxicity of conjugate in presence or absence of GLUT1 inhibitors was determined by MTT assay. Results: We showed that PAMAM-dox-glc conjugate exhibits pH-dependent drug release and increased cytotoxic activity compared to free drug in cells cultured in medium without glucose. Further, we proved that these cells overexpress transporters of GLUT family. The toxic effect of conjugate was eliminated by the application of specific GLUT1 inhibitors. Conclusion: Our findings revealed that the glucose moiety plays a crucial role in the recognition of cells with high expression of GLUT receptors. By selectively blocking GLUT1 transporter we showed its importance for the cytotoxic activity of PAMAM-dox-glc conjugate. These results suggest that PAMAM-glucose formulations may constitute an efficient platform for the specific delivery of anticancer drugs to tumor cells overexpressing transporters of GLUT family.
Publisher Pharmaceutical Research
Wikidata Q92328419
Citation Pharmaceutical Research 36 (2019) UNSP 140
DOI https://doi.org/10.1007/S11095-019-2673-9
Tags

Back to list