Impact of the Core Architecture of Dual pH-Responsive Polymer Nanoparticles on Intracellular Delivery of Doxorubicin

We report the design of dual pH-responsive multicomponent nanoparticles with tunable core polymer architectures to understand how polymer architecture affects intracellular therapeutic delivery. Star and linear core polymers were synthesized using charge shifting monomers, with anticancer drug doxorubicin (Dox) covalently conjugated via hydrazone linkages. Nanoparticles comprising either a star or linear core were designed by self-assembly with an amphiphilic block copolymer. Despite similar physicochemical properties, nanoparticles with a linear core displayed higher toxicity in MCF-7 cells (IC50 = 60 ng/mL) compared to that of the star core (IC50 > 1000 ng/mL), suggesting that polymer architecture influenced drug release behavior.