Although
doxorubicin (DOX) is one of the most used chemotherapeutic drugs due to its efficacy against a wide group of
cancer types, it presents severe side effects. As such, intensive research is being carried out to find new nanoscale systems that can help to overcome this problem.
Polyester dendrimers based on the monomer 2,2-bis(hydroxymethyl)propionic
acid (bis-MPA) are very promising systems for biomedical applications due to their biodegradability properties. In this study, bis-MPA-based
dendrimers were, for the first time, evaluated as DOX delivery vehicles. Generations 4 and 5 of bis-MPA-based
dendrimers with
hydroxyl groups at the surface were used (B-G4-OH and B-G5-OH), together with
dendrimers partially functionalized with
amine groups (B-G4-NH2/
OH and B-G5-NH2/
OH). Partial functionalization was chosen because the main purpose was to compare the effect of different functional groups on
dendrimers'
drug delivery behavior without compromising cell viability, which is often affected by
dendrimers' cationic charge. Results revealed that bis-MPA-based
dendrimers were cytocompatible, independently of the chemical groups that were present at their surface. The B-G4-NH2/
OH and B-G5-NH2/
OH dendrimers were able to retain a higher number of DOX molecules, but the in vitro release of the
drug was faster. On the contrary, the
hydroxyl-terminated
dendrimers exhibited a lower loading capacity but were able to deliver the
drug in a more sustained manner. These results were in accordance with the cytotoxicity studies performed in several models of
cancer cell lines and human mesenchymal stem cells. Overall, the results confirmed that it is possible to tune the
drug delivery properties of bis-MPA-based
dendrimers by modifying surface functionalization. Moreover, molecular modeling studies provided insights into the nature of the interactions established between the
drug and the bis-MPA-based dendrimers─DOX molecules attach to their surface rather than being physically encapsulated.