February 23, 2023

PRUCA Diagnostics: Protease Responsive Ultrasound Contrast Agents for Personalized Healthcare of Patients with Inflammatory Bowel Disease

7th Call, Tech Trans

Short Summary

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are long-term conditions that affect the digestive system. The chronic inflammation and damage to the lining of the intestine cause severe burden for patients and require close monitoring of the disease state to navigate therapy. Commonly, ultrasound (US) is used to image the abdomen and identify fibrotic tissue, however, determining the inflammatory state remains difficult. Here we aim to enhance US-based IBD diagnostics and monitoring by providing a contrast agent that can report molecular activity of inflammation through US. The contrast agent is comprised of lipid microbubbles that alter the US signal upon interaction with certain enzymes involved in inflammation such that a bright image appears.

Goals

We propose the engineering of responsive microbubbles that can be used as biomolecular contrast agents in US imaging to stratify inflamed fibrotic tissue in IBD due to protease activity. Gas-filled microbubbles are frequently used in US imaging to enhance contrast because of their ability to efficiently scatter ultrasound. The Protease Responsive US Contrast Agent (PRUCA) concept we developed is based on gas-filled microbubbles with a lipid shell crosslinked with peptides and equipped with molecular anchors. Once injected into the blood stream, PRUCAs are design to reside in the vessels of fibrotic tissues and the peptide linkers will be broken down by certain targeted protease if the tissue is inflamed. This in turn softens the shell and creates a bright US image that should inform clinicians about the state of inflammation.

Significance

Because sonography is a widely distributed and affordable diagnostic technique that is increasingly used in IBD care, this concept offers a basis for cost-effective and readily translatable instrumentation to improve clinical decision making at the point-of-care.

Background

Proteases are important molecules in health and disease, and their activity provides insight into the state and progression of many ailments, including inflammatory diseases such as IBD. Detection of protease activity at inflamed sites would be a powerful tool for clinicians to support their decision making.