Multifunctional nanoparticles for drug delivery and imaging: Effect of ultrasound on cellular uptake and tumor tissue distribution

This study is focused on cellular uptake (in vitro) and microdistribution (in vivo) using a novel multifunctional drug delivery system consisting of microbubbles (MBs) stabilized by polymeric nanoparticles (NPs). Prostate cancer cells in suspension were incubated with NP-loaded MBs and then exposed to focused ultrasound (US, 300 kHz). Cellular uptake was measured by flow cytometry. To study microdistribution of the NPs in prostate tumors, particles were injected intravenously into mice bearing subcutaneous prostate xenografts. The tumors were exposed to focus US 5 min or 24 h after the injection using 300 kHz or 5 MHz US. Tumors were frozen and sections were analyzed by confocal laser scanning microscope (CLSM). Fluorescent labeled lectin was used to stain the blood vessels. The in vitro study shows enhancement of cellular uptake in the presence of US compared to untreated cells. Cellular uptake of NPs increased with increase in mechanical index. Analysis of confocal images of tumor slices showed an enhanced uptake and improved penetration of NPs after US exposure. These effects might be due to cavitation and radiation forces. The results show the potential of the novel multifunctional drug delivery system to improve cancer therapy.