Fabrication of amino acid conjugated Polymeric Micelles for controlled
anticancer drug delivery using Radiation and pH-stimuli-triggering
systems
Abstract
Drug delivery to the tumor site and minimizing adverse effects on
surrounding tissues remains a fundamental issue. In this study, pH and
radiation-responsive PLGA-PEG-PLGA amphiphilic copolymers were
terminally conjugated with hydrophobic tryptophan (Try), tyrosine (Tyr),
or histidine (His) amino acids (aa). To synthesize the tri-copolymers,
PEG was employed as an initiator and Sn (Oct) 2 as a
catalyst. In this system, micelles were developed with an inner core
comprised of hydrophobic blocks (PLGA and Try/Tyr/His) and PEG as a
hydrophilic corona to improve the stability. The rise in DOX
fluorescence intensity and particle size shift because of light and pH
stimulation supported structural destabilization of the micelle.
Try-PLGA-PEG-PLGA-Try and Tyr-PLGA-PEG-PLGA-Tyr micelles had negligible
cytotoxicity (more than 90% cell viability at 100 g/mL) when incubated
with NIH-3T3 and HeLa cell lines using MTT assays. DOX-loaded micelles
(Try/Tyr), on the other hand, had a greater impact on HeLa cells, with
roughly 30% of cells were survived at a maximum DOX dosage (10 g/mL).
The cellular uptake experiment further verified that DOX-loaded micelles
were internalized in the cytoplasm and nucleus of cancer cells.
Therefore, the prepared copolymer systems have the potential to be
employed as stimuli-responsive carriers for the delivery of anti-cancer
drugs.