Acute effects of ultrasound-targeted microbubble destruction on tumor interstitial fluid pressure and intratumoral distribution of doxorubicin and nab-paclitaxel in an orthotopic breast cancer model

Insufficient drug delivery remains a major challenge in solid tumour therapy. Ultrasound-targeted microbubble destruction (UTMD) can modulate the tumour microenvironment and improve intratumoral drug delivery. This study evaluated the acute effects of UTMD on tumour interstitial fluid pressure (IFP) and the distribution of doxorubicin and nab-paclitaxel in an MCF7-derived orthotopic breast cancer model. IFP was measured approximately 2 min after treatment. Significant IFP reductions were observed in the doxorubicin-USMB, nab-paclitaxel-USMB, and USMB-alone groups, indicating that UTMD itself contributes to the acute pressure response. Fluorescence imaging showed increased doxorubicin-associated signal in both peripheral and central tumour regions after UTMD, whereas Cy5-labeled nab-paclitaxel increased mainly in the tumour periphery. H&E staining revealed vascular dilation, erythrocyte extravasation, and microthrombus formation after USMB treatment. These findings suggest that UTMD reduces tumour IFP and alters intratumoral drug distribution, particularly in peripheral regions. However, because the two drugs differ in multiple physicochemical and formulation properties and antitumour efficacy was not assessed, their distribution differences cannot be attributed solely to size or interpreted as evidence of improved therapeutic efficacy.