Sonodynamic Therapy of Mice Breast Adenocarcinoma with HP-MSN

Abstract

Sonodynamic therapy was appeared as a minimally invasive treatment that is based on the use of low-intensity ultrasound waves with a chemical agent that can be activated by ultrasound (US). The aim of this study was to evaluate the effect of hematoporphyrin (HP) and hematoporphyrin-encapsulated mesoporous silica nanoparticle (HP-MSN) with sonodynamic therapy in an animal model of breast adenocarcinoma. In this study, 96 Balb/C female mice with grafted breast adenocarcinoma were divided to 16 groups each containing 6 mice including: control, sham, HP (2.5 and 5 mg/kg), HP-MSN (2.5 and 5 mg/kg), 3 MHz US (1 and 2 W/cm2), US + HP (2.5 and 5 mg/kg) and US + HP-MSN (2.5 and 5 mg/kg). The tumor relative volume, tumor growth inhibition ratio (TGI), the time of tumor growth (T2 and T5-times) and tumor grading were used to evaluate the treatment outcome. The relative volume parameters and TGI% of 3 MHz US (2 W/cm2) and HP-MSN (5 mg/kg) groups were effective in delaying tumor growth when compared with control and sham at the middle of observation. The time required for tumor to reach two-times (T2) the initial volume in the case of HP-MSN (5 mg/kg) group was greater than that sham and control groups. Analysis of data showed that the groups of US (2 W/cm2) + HP (5 mg/kg), US (1 W/cm2) + HP-MSN (5 mg/kg) and US (2 W/cm2) + HP-MSN (5 mg/kg) indicated antitumor effects from days 18 to 30 after treatment. TGI% in these groups is 54, 45 and 39%, respectively, and the time of T2 and T5 is greater than that in the control and sham. Kaplan–Meier analysis showed that the 45-day survival was 60% for the group treated with US (2 W/cm2) + HP-MSN (5 mg/kg). In histopathological study, all experimental groups had a poorly differentiated grading except of US (2 W/cm2) + HP-MSN (5 mg/kg) group which has a moderately differentiated degree based on Bloom-Richardson classification. Based on the results, we found that sonodynamic therapy with HP-MSN have an antitumor effect on mice breast adenocarcinoma. Conventional treatments for cancer are still far from ideal in terms of systemic toxicity, tumor-selectivity and side effects. Therefore, the development of highly selective and minimally invasive therapies such as sonodynamic therapy is necessary.