Noncovalent Interactions with PAMAM and PPI Dendrimers Promote the Cellular Uptake and Photodynamic Activity of Rose Bengal: The Role of the Dendrimer Structure

Rose bengal is an anionic dye considered as a potential photosensitizer for anticancer photodynamic therapy. The clinical utility of rose bengal is hampered by its short half-life, limited transmembrane transport, aggregation, and self-quenching; consequently, efficient drug carriers that overcome these obstacles are urgently required. In this study, we performed multilevel in vitro and in silico characterization of interactions between rose bengal and cationic poly(amidoamine) (PAMAM) and poly(propyleneimine) (PPI) dendrimers of the third and fourth generation and assessed the ability of the resultant complexes to modulate the photosensitizing properties of the drug. We focused on explaining the molecular basis of this phenomenon and proved that the generation- and structure-dependent binding of the dye by the dendrimers increases the cellular uptake and production of singlet oxygen and intracellular reactive oxygen species, leading to an increase in phototoxicity. We conclude that the application of dendrimer carriers could enable the design of efficient photodynamic therapies based on rose bengal.

Automated summary

In this study, interactions between rose bengal and cationic dendrimers were characterized at multiple levels in vitro and in silico, showing that dendrimers of the third and fourth generation can enhance the photosensitizing properties of the dye by increasing cellular uptake and production of reactive oxygen species. The results suggest that dendrimer carriers could facilitate the development of efficient photodynamic therapies using rose bengal.