Increased intracellular uptake and tissue accumulation of Dox by MbDox+US treatment. A. LL/2 and CT26 cells were treated with indicated formulations at 4 h after treatment. Images of intracellular Dox distribution were collected by confocal microscopy. Dox is indicated by red fluorescence and the nucleus is stained with DAPI (blue, scale bar = 10 μm). B. The intracellular concentration of Dox in LL/2 and CT26 cells after treatment with the indicated formulations was quantified by a microplate reader. C. Tumor-bearing mice were treated with indicated formulations, and tumor tissues and major organs were collected to analyze the Dox concentration by HPLC. Data are expressed as mean ± SEM, * indicates P < 0.05, ** indicates P < 0.001, NS, no significance.