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

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.

Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior

“…However, we always observed particles around 10 nm, representing a dominant fraction corresponding to small clusters containing from several units to high tens of DDM molecules, depending on the generation. The formation of small clusters was also previously reported for other carbosilane glycodendrimers …”

Carbosilane dendritic nanostructures, highly versatile platforms for pharmaceutical applications

“…This indicated that the flexibility of the skeleton and the availability of its hydrophobic interior, as well as the formation of larger assemblies in buffer solution, are key factors for the interaction. In subsequent research, the same authors determined the cytotoxicity toward breast and ovarian cancer cell lines and noncancer BJ cell line (human fibroblast cell type) of several dendrimers bearing glucose, galactose, or oligo(ethyleneglycol)‐modified galactose peripheral units and prepared glycodendrimer–doxorubicin complexes (Figure 5; Mullerova et al, 2022). The results obtained indicated that these systems are suitable candidates for the encapsulation and subsequent release of doxorubicin, which is more efficiently released in acidic environments (tumor conditions) than under physiological conditions (pH 7.4).…”

“…Example of CBS glycodendrimer as drug carrier in antitumor therapy. Reprinted with permission from Mullerova et al (2022). Copyright 2022, American Chemical Society…”

Adaptive Synthesis of Functional Amphiphilic Dendrons as a Novel Approach to Artificial Supramolecular Objects

“…In most cases, the excess reagent is readily separable by using extraction or evaporation. Only in the case of compound-L1-9-bearing dimethylammonium groups, the separation requires organic solvent nanofiltration (OSN) [35][36][37]-an effective method which we previously exploited for the purification of CS-dendrimers [27,28,38,39]. The key feature of synthetic amphiphiles, essential for their investigation in biological environments, is their water-solubility.…”

“…Our long-term interest has been focused on CS dendrimers with a well-defined structure that express multivalent presentation of functional moieties at their periphery [27][28][29][30][31] and, due to the incompatibility of their hydrophobic interior with polar periphery, can be considered as unimolecular micelles [32]. Here we turn our attention to a development of new versatile synthetic protocols for amphiphilic building blocks capable of self-assembly to regular micelles and other supramolecular objects.…”