Carbosilane Glycodendrimers for Anticancer Drug Delivery: Synthetic Route, Characterization, and Biological Effect of Glycodendrimer–Doxorubicin Complexes
Monika Müllerová, Dina Maciel, Nádia Nunes, Dominika Wróbel, Marcel Štofik, Lucie Červenková Šťastná, Alena Krupková, Petra Cuřínová, Kateřina Nováková, Matěj Božík, Marek Malý, Jan Malý, João Rodrigues, Tomáš Strašák
Abstract
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.