pH/redox sensitive nanoparticles with platinum(iv) prodrugs and doxorubicin enhance chemotherapy in ovarian cancer

Abstract

pH/redox sensitive, dual drug loaded nanoparticles were prepared from poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) for improving cancer therapy. Platinum(IV) and cis-aconitic anhydride-doxorubicin (CAD) were anchored to lysine residual amine groups of PLL to form polymer prodrug conjugates, which then self-assembled into nanoparticles with hydrophobic platinum(IV) prodrugs and CAD as the core. The nanoparticles were stable in neutral environments, but once under acidic and reductive conditions, the drugs were rapidly released. The dual-loaded nanoparticles had comparable intracellular toxicity to the regimen of combined application of free cisplatin and doxorubicin.