Carbosilane Glycodendrimers for Anticancer Drug Delivery: Synthetic Route, Characterization, and Biological Effect of Glycodendrimer–Doxorubicin Complexes.

0549972 - ÚCHP 2023 RIV US eng J - Journal Article
Müllerová, Monika - Maciel, D. - Nunes, N. - Wróbel, D. - Štofik, M. - Červenková Šťastná, Lucie - Krupková, Alena - Cuřínová, Petra - Nováková, Kateřina - Božík, M. - Malý, M. - Malý, J. - Rodrigues, J. - Strašák, Tomáš
Carbosilane Glycodendrimers for Anticancer Drug Delivery: Synthetic Route, Characterization, and Biological Effect of Glycodendrimer–Doxorubicin Complexes.
Biomacromolecules. Roč. 23, č. 1 (2022), s. 276-290. ISSN 1525-7797. E-ISSN 1526-4602
R&D Projects: GA ČR(CZ) GA20-21421S; GA MŠMT(CZ) LTC19049
EU Projects: European Commission(XE) CA17140 - COST Action
Grant - others:FCT(PT) UIDB/00674/2020; FCT(PT) UIDP/00674/2020; ARDITI(PT) M1420-01-0145-FEDER-000005-CQM+; FCT(PT) 2020.04679.BD
Institutional support: RVO:67985858 ; RVO:61388963
Keywords : molecular-dynamics * poly(amidoamine) dendrimer * force-field
OECD category: Organic chemistry; Biochemistry and molecular biology (UOCHB-X)
Impact factor: 6.2, year: 2022
Method of publishing: Open access with time embargo

The complexity of drug delivery mechanisms calls for the development of new transport system designs. Here, we report a robust synthetic procedure toward stable glycodendrimer (glyco-DDM) series bearing glucose, galactose, and oligo(ethylene glycol)-modified galactose peripheral units. In vitro cytotoxicity assays showed exceptional biocompatibility of the glyco-DDMs. To demonstrate applicability in drug delivery, the anticancer agent doxorubicin (DOX) was encapsulated in the glyco-DDM structure. The anticancer activity of the resulting glyco-DDM/DOX complexes was evaluated on the noncancerous (BJ) and cancerous (MCF-7 and A2780) cell lines, revealing their promising generation- and concentration-dependent effect. The glyco-DDM/DOX complexes show gradual and pH-dependent DOX release profiles. Fluorescence spectra elucidated the encapsulation process. Confocal fluorescence microscopy demonstrated preferential cancer cell internalization of the glyco-DDM/DOX complexes. The conclusions were supported by computer modeling. Overall, our results are consistent with the assumption that novel glyco-DDMs and their drug complexes are very promising in drug delivery and related applications.
Permanent Link: http://hdl.handle.net/11104/0325853