Combination of anti-angiogenesis treatment and chemotherapy in solid tumors by using drug-loaded nanodroplets vaporization

Ultrasound (US) sonication can vaporize perfluorocarbon droplets into gaseous phase, called acoustic droplet vaporization (ADV). During ADV, the occurring inertial cavitation can burst tumor vessels, improve drug extravasation, and change tumor microenvironments; which provides a potential strategy to simultaneously combine anti-angiogenesis treatment and chemotherapy. Doxorubicin-loaded nanodroplets (DOX-NDs) with a mean size of 373 nm containing 2.49 mg DOX/mL were used in this study. Intravital imaging showed the extravasation area was increased over 5.7-fold by ADV. After combined treatment, tumor perfusion was significantly reduced to 43% and 18% in peripheral and central region, respectively. For histological images, drug extravasation of the DOX-NDs+US group was especially improved 1.2- and 4.7-fold in tumor periphery and center relative to the DOX-NDs group. Tumor sizes decreased 22%, 36%, and 68% for NDs+US, DOX-NDs, and DOX-NDs+US, respectively, to prolong the survival of tumor-bearing mice. Therefore, this study demonstrated that the combination of anti-angiogenesis treatment and chemotherapy with DOX-NDs vaporization promotes uniform treatment to improve therapeutic efficacy.