Completely degradable backbone-type hydrogen peroxide responsive curcumin copolymer: synthesis and synergistic anticancer investigation

Abstract

So far, several different kinds of polymer based drug delivery systems have been developed one after another. However, most of them were focused on physical encapsulation of drugs into hydrophobic micelle cores or covalently linked drug molecules to side chains as prodrugs through cleavable chemical bonds. Herein, using a polycondensation reaction between curcumin, short polyethylene glycol chains, and oxalyl chloride, a backbone-type curcumin and oxalate linkage containing poly(curcumin-co-oxalate) copolymer was synthesized. The resultant copolymer could release active therapeutic agents (curcumin) through hydrogen peroxide (H₂O₂) triggered complete degradation of the main chains, making them perfect controlled drug delivery vehicles and suitable for rapid metabolism. UV-vis and fluorescence experimental results demonstrated that the aqueous dispersible spherical nanoparticles formulated from such copolymers were stable under physiological conditions, but gradually dissociated once exposed to exogenous H₂O₂. Moreover, after encapsulating an additional anti-cancer drug (camptothecin; CPT) and a near infrared photothermal conversion reagent (IR780), CPT/IR780@poly(curcumin-co-oxalate) complex micelles were formed, and the in vitro cell test indicated that they were efficient synergistic chemo-photothermal therapy units. This work fills the gap of the conventional nanocarrier design, and such H₂O₂ responsiveness has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy.