Regulation of drug release performance using mixed doxorubicin-doxorubicin dimer nanoparticles as a pH-triggered drug self-delivery system

A mixed drug self-delivery system (DSDS) with high drug content (>50%) was developed to regulate pH-triggered drug release, based on two doxorubicin (DOX)-DOX dimmers: D-DOX(ADH) and D-DOX(car) conjugated with acid-labile dynamic covalent bonds (hydrazone and carbamate, respectively) and stabilized with PEGylated D-DOX(ADH) (D-DOX(ADH)-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS. Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios. The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates. The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.