Using Ultrasound to Enhance Tumor Cell Killing By Anti-PD1 and Doxorubicin-Loaded Particles

Metastatic melanoma is currently an incurable disease for which alternative treatments to chemotherapy alone are sought. The use of ultrasound (US) with microbubbles is a promising regimen for tumor treatment. In this study, the addition of US provided a means for controlled drug delivery through inertial cavitation. The aim was to obtain a synergistic or additive effect with respect to tumor killing by combining US with chemotherapy and checkpoint blockades. In vitro experiments combining US with blank PLGA particles showed higher cytotoxicity towards B16.F10 melanoma cells compared to either treatment alone. Furthermore, in vitro experiments demonstrated an ability to control the release kinetics of doxorubicin (dox) from dox-loaded PLGA particles through the application of US. Utilizing a melanoma murine model, the application of US to dox-loaded particles and/or anti-programmed cell death protein 1 (anti-PD1) yielded higher tumor regressions and survival rates compared to any treatment alone.