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

Summary

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 contrast agents with the following properties:

  • Nanoparticle size down to 50 nm, allowing for increased accumulation within tumors.
  • Contrast imaging at concentrations as low as 2.5 ug/mL, which may improve their safety in clinical applications, compared to currently used contrast nanoparticles.
  • High acoustic activity, with mechanical indices as low as 0.7, which is well below the FDA limit (1.9).
  • Compatible with conventional medical ultrasound instruments specialized for a variety of organs.
  • Customizable with the ability to select for particle size and shape as well as the choice of stabilizer.
  • Biodegradable, improving safety for in vivo imaging.
  • Utility for imaging with standard ultrasound equipment, and tumor ablation with high-intensity focused ultrasound.

 

Publications

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

Sabuncu et al., “Protein-Coated Biodegradable Gas-Stabilizing Nanoparticles for Cancer Therapy and Diagnosis Using Focused Ultrasound” Adv Mat Interfaces 10(2022). Link

Sabuncu et al., “Ultrafast Background-Free Ultrasound Imaging Using Blinking Nanoparticles” Nano Lett. 23 (2023): 659-666. Link

 

Licensing Opportunity

This technology is available for licensing.

 

Inventors:

Patents

Published United States WO 2022/056035
Published United States US 2023/0355812 A1
Published European Patent Convention EP4210754

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