N-doping of the TiO2/C nanostructure derived from metal-organic frameworks with high drug loading for efficient sonodynamic & chemotherapy

Abstract

Therapeutic agents can be effectively used for clinically treating cancer rely on critically enhancing their efficacy in the tumor microenvironment under hypoxic conditions. Sonodynamic therapy is a promising strategy for treating cancer that complies with all the requisites of penetrating the deep tissues without inflicting additional trauma. However, the hypoxic tumor microenvironment is not conducive to the sonodynamic therapeutic reagents. This study procured the N-doped TiO2/C nanocomposites by calcining the Ti-containing metal-organic frameworks. Further, the N-doped TiO2/C-PEG was successfully equipped with Tirapazamine (TPZ) with a high drug loading capacity and the sonodynamic effect was found to be better than the TiO2/C due to the smaller bandgap. Further, the N-doped TiO2/C-PEG was successfully equipped with Tirapazamine (TPZ) with a high drug-loading capacity. The resultant N-TiO2/C-PEG@TPZ nanoparticles were found to exhibit high blood circulation stability, responsive drug release, and outstanding efficiency in case of the sonodynamic therapy and chemotherapy. The N-TiO2/C-PEG was also significantly bio-compatible with no obvious toxicity and damage to the blood and major organs of the mice. These preclinical experiments, therefore, substantiated N-TiO2/C-PEG@TPZ to possess an excellent therapeutic effect. Hence, this work can provide a valuable multi-modal treatment method for overcoming the hypoxic microenvironment of the tumors.

Keywords

• Metal-organic frameworks
• Sonodynamic therapy
• Chemotherapy
• Hypoxic environment
• N-doped TiO2