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Advisor(s)
Abstract(s)
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 dendrimersDOX molecules attach to their surface rather than being physically encapsulated.
Description
Keywords
Cells Dendrons Functionalization Molecules Toxicity . Faculdade de Ciências Exatas e da Engenharia Centro de Química da Madeira
Citation
Gonçalves, M., Kairys, V., Rodrigues, J., & Tomás, H. (2021). Polyester Dendrimers Based on Bis-MPA for Doxorubicin Delivery. Biomacromolecules, 23(1), 20-33.
Publisher
American Chemical Society