Preparation of doxorubicin-loaded metallic organic nanoparticles and their effect for enhancing efficacy of high-intensity focused ultrasound therapy in tumor-bearing mice

Abstract

To prepare metallic organic nanoparticles that produce synergistic effect in high-intensity focused ultrasound (HIFU) therapy of tumors. Glucose oxidase (GOD), MnO2, ferric iron (Fe3+) and doxorubicin (DOX) were self-assembled by physical adsorption with previously prepared manganese dioxide (MnO2) nanoparticles to obtain GOD-MnO2-Fe3+-DOX nanoparticles (GMFD NPs). HepG2 tumor-bearing nude mouse models were given intravenous injections of normal saline or GMFD NPs followed 4 h later by HIFU at the acoustic power of 90 W with a total treatment time of 3 s. The changes of tumor gray value before and after HIFU irradiation were observed and 24 h after HIFU irradiation, coagulation necrosis in the tumor tissues was examined; the histological changes of the tumor tissues were observed with HE staining. We successfully prepared GMFD NPs, which had an average particle size of 131.23±0.84 nm with a surface potential of 21.87±1.72 mV. GMFD NPs, with a drug loading rate of 40.18%, was capable of releasing more than 77.2% of the loaded DOX within 4 h in acidic environment. In the tumor-bearing mouse models, HIFU irradiation following GMFD NP injection, as compared with saline injection, resulted in significantly enhanced gray value of the tumor (25.5±4.5 vs 18.7±3.9, P=0.04) and greater volume of coagulation necrosis (105.80 ± 1.21 mm3 vs 38.02 ± 0.34 mm3). The energy efficiency factor (EEF) was significantly lower in GMFD NPs group than in saline group (1.79 vs 4.97, P < 0.001). GMFD NPs prepared in this study can enhance tumor ablation efficacy of HIFU and release DOX for further treatment of the residual tumor tissue in mice.