Ultrasound-guided liposomes boost imaging, target drug/gene therapy

One of the newest tools in the diagnosis and treatment of cardiovascular disease and stroke combines a 40-year-old imaging technique and liposomes, little globules of soluble fats and water that circulate naturally throughout the bloodstream.

The technique, developed by Northwestern University researcher David D. McPherson, M.D., and colleagues with a $2.3 million grant from the National Institutes of Health, uses ultrasound energy to create microbubbles inside specially treated liposomes and then direct the liposomes to specific targets, such as atherosclerotic plaques or blood clots, in the coronary arteries and other arteries in the body, including those to the brain.

Once they reach their target in the arteries, the echogenic liposomes, or ELIPs, produce an acoustic shadow that improves ultrasound’s ability to visualize and diagnose the extent of plaques or clots within the arteries.

Further, the ELIPs can be treated to also encapsulate certain drugs, such as antibiotics or thrombolytic (clot-busting) drugs or gene therapy, which, with the help of ultrasonic pulses, can be released at the site of a plaque or a clot or into living cells. This is caused by cavitation, the ability of the ultrasound to increase the energy of the microbubble, which then opens the cell membrane and allows drugs to enter.

McPherson, who is Lester B. and Frances T. Knight Professor of Cardiology and professor of medicine at the Feinberg School of Medicine at Northwestern University, believes that the ultrasound technique may further understanding of how atherosclerotic plaques develop and grow, as well as enhance more than tenfold scientists’ ability to target drug or gene therapy toward specific atherosclerotic components or affected tissue without damaging cells.

“The science of ultrasound, in addition to its imaging capability, also lies in its biologic effects. By harnessing the physical effects of ultrasound, we can physiologically evaluate and therapeutically affect vascular and biologic tissue,” said McPherson, who is conducting the ultrasound/liposome research with scientists from Northwestern and the University of Cincinnati.

“While our research is in the early stages, we believe that our combined technology will have far-reaching implications in humans, allowing for more directed atherosclerotic and thrombolytic therapy,” McPherson said.

Ultrasonography is a 40-year-old noninvasive, two-dimensional imaging technique used to examine and measure internal body structures and to detect body abnormalities. In cardiology, ultrasound is used to see inside the heart to identify abnormal structures or functions, for example, to measure blood flow through heart and in major blood vessels.

Liposomes are used in the cosmetic industry to transport small molecules into cells. The liposome wall is similar in composition to the material of cell membranes. This enables liposomes to merge readily with cellular membranes and release molecules into cells.

Collaborating with McPherson on the ultrasound/liposome research are Christy Holland, University of Cincinnati; and Shao-Ling Huang, Bonnie J. Kane, Robert C. McDonald, Ashwin Nagaraj, Sanford I. Roth and Susan D. Tiukinhoy, Northwestern University.