The toxicity performance of pH-responsive doxorubicin nanocarrier with different drug loading strategy

To improve the water solubility, keep drug loading rate and reduce toxic side effects of chemotherapeutic drugs, two kinds of pH–responsive nanoparticles (denoted as HDOX and PDOX) were prepared to achieve controlled release of drugs and their toxicity against tumor cells were studied. The HDOX was synthesized to incorporate doxorubicin (DOX) via a pH-responsive chemical hydrazone bond, while the PDOX was a pH-responsive polymer-coated nanoparticle to load DOX. The drug loading was measured by fluorescence spectroscopy. The drug release performances in vitro were investigated under different simulated conditions, as well as the toxicity of two NPs were evaluated by the MTT assay. In vitro experiments showed that HDOX (∼15 wt %) has a superior drug-loading ratio compared to PDOX (∼10 wt %). Besides, HDOX and PDOX also displayed a higher stability in normal physiological environment. After the nanoparticles were internalized by the tumor cells, the nanoparticles could transport to the entire tumor cells and showed a pH-responsive drug release behavior. In vivo experiments confirmed excellent biological safety of the two nanoparticles. These results demonstrated that nanocarrier-based chemical bonding strategy provided advantages for the development pH-responsive nanomedicine for cancer therapy.