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-DOXADHand D-DOXcarconjugated with acid-labile dynamic covalent bonds（hydrazone and carbamate, respectively） and stabilized with PEGylated D-DOXADH(D-DOXADH-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, p H-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.