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

We report the design of dual pH-responsive multicomponentnanoparticleswith tunable core polymer architectures to understand how polymerarchitecture affects intracellular therapeutic delivery. Star andlinear core polymers were synthesized using charge shifting monomers,with anticancer drug doxorubicin (Dox) covalently conjugated via hydrazonelinkages. Nanoparticles comprising either a star or linear core weredesigned by self-assembly with an amphiphilic block copolymer. Despitesimilar physicochemical properties, nanoparticles with a linear coredisplayed 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.

Automated summary

We designed dual pH-responsive multicomponent nanoparticles with tunable core polymer architectures to investigate the effect of polymer architecture on intracellular therapeutic delivery. The nanoparticles were assembled using amphiphilic block copolymers and contained doxorubicin (Dox) covalently conjugated to star or linear core polymers. Despite similar physicochemical properties, the nanoparticles with a linear core showed higher toxicity in MCF-7 cells (IC50 = 60 ng/mL) compared to those with a star core (IC50 > 1000 ng/mL), suggesting that polymer architecture influenced drug release behavior.