Abstract 5800: Ultrasound-mediated nano-drug delivery system to enhance cancer treatment efficacy: An in vitro study

Abstract Conventional non-targeted nano-sized drug delivery systems face limitations such as restricted drug penetration depth and treatment efficacy in solid tumors. External stimulus such as ultrasound waves can trigger targeted, on-demand drug release from the nanocarriers. We demonstrate a first-of-its-kind use of low-intensity pulsed ultrasound (LIPUS) to induce Doxorubicin release from the surface of gold nanoparticle drug carriers. Our 1-MHz LIPUS beam is capable of penetrating tissue to sufficient depths with the required power/intensity for drug release applications with a nominal intensity of around 3 W/cm2 in the region of interest (ROI). This level of intensity is necessary to elevate the tissue temperature to the mild hyperthermia range of 41 to 45 °C. Our in vitro experiments demonstrate a remarkable 22% enhancement in drug release with the addition of LIPUS. Measurements of drug release kinetics, with and without LIPUS, suggest that LIPUS shifts the drug release mechanisms from static (Fickian) to dynamic (non-Fickian) release in vitro. Thus, revealing the intricate interactions between ultrasound and drug release from gold nanoparticle drug carriers. To assess the efficacy of the delivery system, we developed an in vitro cell culture model with a customized ultrasound exposure setup. The LIPUS device was situated at the bottom base of a water tank, directing ultrasound beam upward toward a region of interest where the MDA-MB-231 breast cancer cells were located 35 mm away from the LIPUS element. We found that the LIPUS device operating at an acoustic power of around 4 W increased cell killing efficacy by approximately 15% ± 2% when compared to conventional nano-drug delivery, highlighting a significant improvement attributed to ultrasound-induced mechanical effects. At the cellular level, these results underscore the potential advantages of ultrasound-mediated nano-drug delivery over conventional chemotherapy and non-targeted nano-drug delivery. Citation Format: Farshad Moradi Kashkooli, Anshuman Jakhmola, Tyler K. Hornsby, Graham A. Ferrier, Jahangir (Jahan) Tavakkoli, Michael C. Kolios. Ultrasound-mediated nano-drug delivery system to enhance cancer treatment efficacy: An in vitro study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5800.