Ultrasound-mediated nano drug delivery for treating cancer: Fundamental physics to future directions

Integrating Therapeutic Ultrasound With Nanosized Drug Delivery Systems in the Battle Against Cancer

“…TUS-nanoparticle interaction generally involves a combination of mechanical agitation and controlled heating, leading to enhanced drug release and targeted delivery. 1,4,6 In addition, various types of ultrasound-sensitive nanoparticles can be designed to enable controlled drug release or other therapeutic effects in the ROI. Various nanoplatforms are available for developing target-specific TUS-activated NSDDSs, which can be distinguished based on their chemistry and biodegradability.…”

“…4 Thermal interactions arise from the transformation of acoustic energy to thermal energy, resulting in a volumetric temperature rise in the ROI. 2,4,7,9 Acoustic streaming occurs for a large range of ultrasound intensities, while acoustic cavitation typically occurs at high intensities when using TUS exposures with high mechanical indexes. 10 Therapeutic ultrasound typically incorporates one of 3 noninvasive approaches for drug delivery, specifically focusing on drug release triggered by the ultrasound field: low-intensity pulsed ultrasound (LIPUS), low-intensity focused ultrasound (LIFU), and high-intensity focused ultrasound (HIFU).…”

“…17 Delivery of ultrasound-induced hyperthermia, with a compatible modality (such as chemotherapy), should be customized to align with specific treatment objectives. 4…”

“…13,14 Multiple cell lines, involving leukemia, breast cancer, colon adenocarcinoma, ovarian carcinoma, and colorectal carcinoma have also been studied in in vitro preclinical experiments. 1,4,23 In addition, in vivo preclinical trials have been carried out on various cancer types, such as pancreatic, breast, colon, lymphoma, prostate, and ovarian cancers. 1,4,23 These studies have explored the influence of both mechanical and thermal effects induced by LIFU, HIFU, FUS, and LIPUS.…”

Ultrasound meets the cell membrane: for enhanced endocytosis and drug delivery

“…17,18 US-generated mechanical effects, such as microstreaming and shear forces, alter the physical properties of cells and extracellular matrixes, create transient pores in cell membranes, and promote drug uptake; such a phenomenon is called sonoporation. 19–21 On the one hand, sonoporation forms membrane pores that result in a direct inward drug flow and affects the ion pumps on the membrane surface to reduce its outward drug excretion. 22 On the other hand, the artificial addition of microbubbles can lower the threshold of US-induced cavitation, thus enhancing the efficiency and positively influencing the endocytic behavior of cells.…”