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Applying ultrasound in conjunction with microbubbles at the tumor site can enhance vascular permeability and motivate nanoparticle extravasation. We combine low intensity ultrasound (US) and microbubbles (MB) with drug-bearing nanocapsules (NC) to improve the therapeutic index of paclitaxel. Female mice bearing 4T1 mammary carcinoma tumors received one of five treatments: paclitaxel NC only at 2.5 mg/kg; paclitaxel NC only at 5 mg/kg; paclitaxel NC (2.5 mg/kg) prior to two minutes of therapeutic US exposure; paclitaxel NC (2.5 mg/kg) co-administered with MB prior to two minutes of therapeutic US; and control. Therapeutic US was applied using a Sonicator 740 system operated at 1 MHz, 2 W/cm2, and 10% duty cycle. At 2.5 mg/kg, mice treated with NC+MB+US had slower tumor growth compared to treatment with NC or NC+US. A statistically significant difference between NC+MB+US and both NC and NC+US groups was seen on multiple days. Data suggest treating at a dose of 2.5 mg/kg with NC+MB+US is as effective as treating with NC alone at 5 mg/kg. This finding is significant because lowering a treatment dose may reduce the risk of unwanted side effects.