Sonoprinting Nanoparticles on Cellular Spheroids via Surface Acoustic Waves for Enhanced Nanotherapeutics Delivery

Abstract Nanotherapeutics, on their path to the target tissues, face numerous physicochemical hindrances that affect their therapeutic efficacy. These barriers can limit the penetration of nanocarriers into deeper regions of densely packed tissues such as tumors, thereby preventing the efficient delivery of drug cargo. To address this challenge, we introduce a novel approach that employs surface acoustic wave (SAW) technology to sonoprint and enhance the delivery of nanoparticles to spheroids. Our SAW platform is designed to generate focused and unidirectional acoustic waves for creating vigorous acoustic streaming and Bjerknes forces. The effect of SAW excitation on cell viability as well as the accumulation and penetration of nanoparticles on human breast cancer (MCF 7) and mouse melanoma (YUMM 1.7) spheroids were investigated. The high frequency, low input voltage, and contact-free nature of the proposed SAW system ensured over 92% cells’ viability. The SAW sonoprinting enhanced the accumulation of 100 nm polystyrene particles on the spheroids to near four-fold, while improving the penetration of nanoparticles into the spheroids by up to three times. To demonstrate the effectiveness of our SAW platform for nanotherapeutics delivery, the platform was used to deliver nanoliposomes encapsulated with the anti-cancer copper diethyldithiocarbamate (CuET) to MCF 7 and YUMM 1.7 spheroids. A three-fold increase in the cytotoxic activity of the drug was observed in spheroids under SAW, compared to controls. The capacity of SAW-based devices to be manufactured as minuscule wearable patches can offer highly controllable, localized, and continuous acoustic waves to enhance drug delivery efficiency to target tissues.