Reduction-responsive cationic bolaamphiphile vesicles as a versatile platform for photodynamic and chemotherapeutic delivery.
TL;DR
These pyridinium-based bolaamphiphilic vesicles represent a versatile redox-responsive delivery platform capable of enhancing intracellular delivery and therapeutic performance of both photosensitizers and poorly water-soluble anticancer drugs.
Abstract
A reduction-sensitive cationic bolaamphiphile bearing N-methylpyridinium terminal groups and a central disulfide bridge was synthesized and shown to self-assemble in water into stable vesicles with diameters of 200-250 nm. The vesicles undergo redox-triggered disassembly in the presence of tris(2-carboxyethyl)phosphine (TCEP), and analogous behavior was also observed using glutathione (GSH), supporting their responsiveness to reductive environments. Their potential as nanocarriers was evaluated using the photosensitizer Rose Bengal (RB) and the chemotherapeutic agents paclitaxel (PTX) and camptothecin (CPT) in A549, HT29, and MCF7 cancer cell lines. The vesicles significantly enhanced the cellular uptake of RB, as demonstrated by flow cytometry and confocal microscopy. Colocalization analysis with MitoTracker Green further supported preferential mitochondrial localization of RB fluorescence. This was accompanied by a pronounced increase in photodynamic activity upon light irradiation in A549 and MCF7 cells, where apoptosis was identified as the dominant cell-death pathway. In addition, vesicle-based formulations of PTX and CPT improved their cytotoxicity across all tested cell lines, with a particularly strong effect observed in HT29 cells under the experimental conditions employed. Overall, these pyridinium-based bolaamphiphilic vesicles represent a versatile redox-responsive delivery platform capable of enhancing intracellular delivery and therapeutic performance of both photosensitizers and poorly water-soluble anticancer drugs.