Sugar Modification Enhances Cytotoxic Activity of PAMAM-Doxorubicin Conjugate in Glucose-Deprived MCF-7 Cells – Possible Role of GLUT1 Transporter

dc.bibliographicCitation.firstPage140eng
dc.bibliographicCitation.issue10eng
dc.bibliographicCitation.volume36eng
dc.contributor.authorSztandera, Krzysztof
dc.contributor.authorDziałak, Paula
dc.contributor.authorMarcinkowska, Monika
dc.contributor.authorStańczyk, Maciej
dc.contributor.authorGorzkiewicz, Michał
dc.contributor.authorJanaszewska, Anna
dc.contributor.authorKlajnert-Maculewicz, Barbara
dc.date.accessioned2021-12-02T05:51:17Z
dc.date.available2021-12-02T05:51:17Z
dc.date.issued2019
dc.description.abstractPurpose: 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. © 2019, The Author(s).eng
dc.description.versionpublishedVersioneng
dc.identifier.urihttps://oa.tib.eu/renate/handle/123456789/7591
dc.identifier.urihttps://doi.org/10.34657/6638
dc.language.isoengeng
dc.publisherDordrecht [u.a.] : Springer Science + Business Media B.Veng
dc.relation.doihttps://doi.org/10.1007/s11095-019-2673-9
dc.relation.essn1573-904X
dc.relation.ispartofseriesPharmaceutical research 36 (2019), Nr. 10eng
dc.rights.licenseCC BY 4.0 Unportedeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/eng
dc.subjectdoxorubicineng
dc.subjectglucoseeng
dc.subjectglucose transporterseng
dc.subjectPAMAM dendrimereng
dc.subjecttumor targetingeng
dc.subject.ddc610eng
dc.titleSugar Modification Enhances Cytotoxic Activity of PAMAM-Doxorubicin Conjugate in Glucose-Deprived MCF-7 Cells – Possible Role of GLUT1 Transportereng
dc.typearticleeng
dc.typeTexteng
dcterms.bibliographicCitation.journalTitlePharmaceutical researcheng
tib.accessRightsopenAccesseng
wgl.contributorIPFeng
wgl.subjectMedizin, Gesundheiteng
wgl.typeZeitschriftenartikeleng
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