Nanocarriers responsive to glutathione (GSH), a molecule overexpressed in cancer cells, are extensively investigated for the delivery of Pt-based chemotherapeutics for cancer treatment. However, a non-precise control over the conjugation of Pt-based drugs to the side chain of polymers can induce batch-to-batch variations of drug loading and release profiles. Herein, we prepare a GSH-responsive and self-immolative polyprodrug with 61 wt% Pt-based drug in the polymer backbone. The polymer is processed as nanoparticles (diameter < 100 nm) stabilized with a surfactant with a folate moiety, serving as cancer targeting agent. The nanoparticles display a high drug loading (18 wt%) and an efficient redox-responsive release, i.e. 100% release of drug in 10 mM GSH after 3 days. The cytotoxicity of polyprodrug nanoparticles is very high against cancer cells but particularly low against cancer cells treated with a GSH scavenger or normal fibroblast cells, making the polyprodrug nanoparticles suitable nanocarriers for cancer therapy.
