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OHSU # 2823 — Nanoparticle ultrasound contrast agents with high acoustic activity


Contrast-enhanced ultrasound allows for low-cost minimally-invasive imaging; however, the size of typical contrast reagents prevents them from penetrating tumors thereby limiting their utility for cancer diagnostic and therapeutic purposes (theranostics). Oregon Health & Science University (OHSU) researchers have developed novel nanoparticle contrast agents that can be prepared at large scale, utilized at low concentrations and used in both research and clinical applications with standard ultrasound equipment.

Technology Overview

Contrast-enhanced is a cost-effective imaging technique that allows for localized measurements of blood flow or therapeutics delivery. The most commonly used ultrasound contrast agents are microbubbles, but these are not ideal for cancer theranostic purposes because they are too large to leave the vascular space and have poor stability. Smaller, nanoscale contrast particles (nanoparticles) have recently been described, but these agents are either limited by their high serum concentration requirements, which could negatively impact safety in clinical applications, or the need for high acoustic pressures, which are not achievable on standard equipment. To overcome these limitations, Dr. Adem Yildirim and colleagues have developed a novel method of generating contrast nanoparticles that are 50 nm in size. Importantly, these novel nanoparticles can achieve ultrasound contrast at particle concentrations as low as 2.5 ug/mL, which may improve their safety in clinical applications, compared to currently used contrast nanoparticles. Testing these nanoparticles found they required very low acoustic pressure to burst, with mechanical indices as low as 0.7, which is well below the FDA limit (1.9) and can be easily achieved with conventional medical ultrasound instruments specialized for a variety of organs. These novel agents also allow for versatility in the selection of particle size and shape as well as the choice of stabilizer, providing the ability to customize the contrast agent for specific applications. In vitro testing of the nanoparticles also found this agent underwent complete biodegradation following one week in simulated body fluid at 37 °C, offering a potential significant advantage over non-biodegradable nanoscale imaging particles, such as inorganic quantum dots, in in vivo applications. Together, this nanoparticle contrast agent could be implemented at low concentrations with standard equipment to improve the utility of contrast-enhanced ultrasound imaging for nanoscale applications.



Mira et al., “Gas-stabilizing sub-100 nm mesoporous silica nanoparticles for ultrasound theranostics.” ACS Omega 5(2020):24762-24772.


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Published United States WO 2022/056035