Carbosilane Glycodendrimers for Anticancer Drug Delivery:
Synthetic Route, Characterization, and Biological Effect of Glycodendrimer–Doxorubicin
Complexes
posted on 2021-12-20, 14:38authored byMonika Müllerová, Dina Maciel, Nádia Nunes, Dominika Wrobel, Marcel Stofik, Lucie Červenková Št́astná, Alena Krupková, Petra Cuřínová, Kateřina Nováková, Matěj Božík, Marek Malý, Jan Malý, João Rodrigues, Tomáš Strašák
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.