Fabrication of amino acid conjugated polymeric micelles for controlled anticancer drug delivery using radiation and pH-stimuli-triggering systems

Drug delivery to the tumor site and the minimization of adverse effects on surrounding tissues remain major issues in pharmaceutical research. In this study, pH- and radiation-responsive PLGA-PEG-PLGA amphiphilic copolymers were terminally conjugated with tryptophan (Try), tyrosine (Tyr), or histidine (His), utilizing PEG as an initiator and Sn (Oct) 2 as a catalyst. Micelles having an inner core of hydrophobic blocks (PLGA and Try/Tyr/His) and a corona of hydrophilic PEG were developed to improve stability. The structural destabilization of the micelles caused by radiation and pH was characterized by an increase in DOX fluorescence intensities and a shift in particle size. Both Try-PLGA-PEG-PLGA-Try and Tyr-PLGA-PEG-PLGA-Tyr micelles displayed low cytotoxicity in MTT experiments with NIH-3T3 and HeLa cell lines at 100 μg/mL concentrations, with cell viabilities of more than 95.33% and 92.33%, respectively. Samples containing 10 μg/mL DOX, on the other hand, demonstrated significant anticancer efficacy against HeLa cells (28.54% and 29.97% of the cells remained viable after treatment with Tyr and Try, respectively). The cellular uptake experiment also revealed that DOX-loaded micelles were up taken by the cell and that irradiation and pH-sensitive stimuli induced drug release in the cytoplasm and nucleus of the cancer cell. Finally, these findings imply that the synthesized copolymers could be used as stimuli-responsive carriers for anti-cancer drug delivery. [Display omitted] •The amphiphilic polymer, PLGA-PEG-PLGA, undergo self-assembly to form a micelle.•The terminally conjugated amino acids further improved the stability of micelles.•Promising dual-responsive carriers for cancer therapy were developed.•The micelles exhibit anti-proliferative activity against HeLa cell lines.