Focused Ultrasound-mediated Disruption of Plasma Protein Binding Enhances Chemotherapeutic Effects of Paclitaxel on Xenografted Ovarian Cancer in Mice
Paclitaxel (PTX), a widely-used chemotherapeutic agent, exhibits a high rate of plasma protein binding, which severely limits its bioavailability and reduces therapeutic efficacy. This study explored a novel strategy using low-intensity, non-thermal focused ultrasound (FUS) to locally disrupt PTX-albumin binding, thereby enhancing drug delivery and tumoricidal efficacy at tumor sites without increasing systemic toxicity. We applied sonication (600 kHz) with varying pulse durations and duty cycles to OVCAR3 cell constructs The sonication parameters (70% duty cycle and 100 ms pulse duration), applied using 3 W/cm FUS can reversibly unbind PTX from albumin, increasing its bioavailability specifically at tumor sites. This targeted approach enhances chemotherapeutic effectiveness without elevating systemic toxicity or causing off-target damage, highlighting FUS as a promising adjuvant strategy for improving anticancer drug delivery in solid tumors.