Abstract

Targeted delivery of anticancer agents remains a central challenge in modern oncology. This study presents the development of pH-responsive polymeric micelles using poly(ethylene glycol)-block-poly(histidine) (PEG-b-PHis) for the controlled delivery of doxorubicin (DOX) to acidic tumor microenvironments. The micelles demonstrated stability at physiological pH (7.4) and rapid drug release under mildly acidic conditions (pH 6.5). Physicochemical characterization revealed an average diameter of 85.3 ± 4.6 nm, zeta potential of -6.1 ± 0.9 mV, and high drug encapsulation efficiency (>92%). In vitro cytotoxicity assays on MCF-7 and HeLa cells indicated enhanced DOX activity from micelles under acidic pH. Confocal microscopy showed efficient cellular uptake and DOX nuclear localization. In vivo antitumor efficacy in xenograft-bearing mice confirmed superior tumor inhibition and reduced systemic toxicity compared to free DOX. These findings highlight the potential of pH-responsive polymeric micelles in achieving site-specific drug release and improved therapeutic outcomes.