Amphiphilic curcumin conjugate-forming nanoparticles as anticancer prodrug and drug carriers: in vitro and in vivo effects

Curcumin has been shown to have high cytotoxicity towards various cancer cell lines, but its water insolubility and instability make its bioavailability exceedingly low and, thus, it is generally inactive in in vivo anticancer tests. Here, we report an intracellular-labile amphiphilic surfactant-like curcumin prodrug – curcumin conjugated with two short oligo(ethylene glycol) (Curc-OEG) chains via β-thioester bonds that are labile in the presence of intracellular glutathione and esterase. Curc-OEG formed stable nanoparticles in aqueous conditions and served two roles – as an anticancer prodrug and a drug carrier. As an anticancer prodrug, the formed nanoparticles had a high and fixed curcumin-loading content of 25.3 wt%, and released active curcumin in the intracellular environment. Curc-OEG had high inhibition ability to several cancer cell lines due to apoptosis. Intravenously injected Curc-OEG significantly reduced the tumor weights and tumor numbers in the athymic mice xenografted with intraperitoneal...