In vivo evaluation of Sono-chemo therapy via hollow gold nanoshells conjugated to mitoxantrone on breast cancer.

Abstract

Conventional methods of cancer treatment include surgery, chemotherapy, radiation therapy, and immunotherapy. Chemotherapy, as one of the main methods of cancer treatment, due to the lack of targeted distribution of the drug in tumor tissues, is not able to destroy cancer cells and also affects healthy tissues and causes serious side effects in patients. Sonodynamic therapy (SDT) is a promising strategy for non-invasive treatment of deep solid cancer tumors. In this study, for the first time, the sono-sensitive activity of mitoxantrone was investigated and then mitoxantrone (MTX) was conjugated to hollow gold nanostructure (HGN) to improve the efficiency of in vivo SDT. Firstly, after the synthesis of hollow gold nanoshells and the PEGylation process, conjugation of MTX was performed. Then, after evaluating the toxicity of the treatment groups in vitro, in order to perform an in vivo study, 56 male Balb/c mice that had been tumorized by subcutaneous injection of 4T1 cells were divided into eight groups of breast tumor model. Ultrasonic irradiation (US) conditions including intensity of 1.5 W/cm2 (with a frequency of 800 kHz, 5 min), MTX concentration of 2 μM, and HGN dose of 2.5 mg/kg (unit of animal weight) were used. The results show that administration of PEG-HGN-MTX caused a slight reduction in tumor size and growth compared with free MTX. Ultrasound also improved the therapeutic effect of the gold nanoshell in treated groups, and the HGN-PEG-MTX-US treated groups were able to significantly reduce and control tumor size and growth. The findings also show that MTX and HGN can be used as sonosensitizers in SDT. Also, HGN-PEG-MTX can act as a sono-chemotherapy agent for the combination of sonodynamic therapy and chemotherapy for in vivo breast tumors.