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Purpose: According to the side effects of invasive cancer treatments, Sonodynamic Therapy (SDT) as a noninvasive method for breast adenocarcinoma was considered. Sonosensitizer agents’ encapsulation can improve the accumulation of these drugs in the tumor tissue and reduce treatment side effects. Hence, mice breast adenocarcinoma SDT with Hematoporphyrin (HP) and HP-encapsulated Mesoporous Silica Nanoparticles (HP-MSNs) was carried out. Materials and Methods: Ninety-six female breast adenocarcinoma grafted Balb/C mice were randomly divided into 16 groups (n = 6): control, sham, HP, HP-MSN, Ultrasound (US), SDT+HP, and SDT+HP-MSN groups. Sonosensitizer agents were injected intraperitoneally (2.5 or 5 mg/kg, 0.2 ml) 24h before an US radiation (1MHz, 1 or 2 W/cm2, 60 sec). The tumor growth parameters were evaluated 30 days after SDT. Results: The inhibition ratio was enhanced by 23, 18, 18, and 16% relative to the control group in HP-MSN (5 mg/kg), HP-MSN (2.5 mg/kg) HP (5 mg/kg) and US (2 W/cm2) groups, respectively, at 18 days after the injection time; whereas, the analysis of findings revealed an antitumor effect in SDT with HP-MSN groups. The Tumor Growth Inhibition (TGI) percentages were 45, 42, and 42% for the SDT (2 W/cm2) + HP-MSN (5 mg/kg), SDT (1 W/cm2) + HP-MSN (5 mg/kg), and SDT (2 W/cm2) + HP (2.5 mg/kg) groups, respectively, on the 18th day post-injection, and T2 and T5 times were higher than that of control and sham groups (P |