Nanoparticles Highlight Organ Transplant Rejection Through Fluorescent Urine

Researchers at Georgia Tech have developed a sophisticated nanoparticle that can alert clinicians to the early stages of transplanted organ immune rejection through a simple urine test. The nanoparticles can accumulate in transplanted organs and detect immune rejection, whereupon they release molecules that turn the urine of the organ recipient fluorescent. Using a simple urine test, clinicians can then assess if organ rejection is happening, potentially replacing the need for invasive biopsies.

Organ transplantation provides organ recipients with a new lease of life, but it is not without risks and complications. One of the most serious is immune rejection. At present, it is difficult to detect whether immune rejection is occurring early in the process. Often, clinicians don’t realize it has happened until significant organ damage has already occurred. Organ biopsies are risk-prone and invasive, and often don’t indicate whether early-stage immune rejection is occurring.

“The biopsy is not predictive. It’s a static snapshot. It’s like looking at a photo of people in mid-jump,” explains Gabe Kwong, a researcher involved in the study. “You don’t know if they’re on their way up or on their way down. With a biopsy, you don’t know whether rejection is progressing or regressing.”

Spotting immune rejection at its early stages and tracking the immune response over time could allow clinicians to modify the dose of immunosuppressants someone receives, potentially preventing or reducing organ damage. To achieve this, the Georgia Tech researchers developed a new type of nanoparticle that is delivered intravenously, and can accumulate in transplanted organs.

The particles consist of an iron oxide core coated with amino acid bristles that have fluorescent molecules at their tips. When T cells release a specific enzyme involved in the early stages of immune rejection in the vicinity of a nanoparticle, it cleaves the bristles and releases the fluorescent molecules, which travel through the bloodstream and end up in the urine.

So far, the researchers have tested the system in mice that received small skin grafts. Early stage immune rejection meant that the animals’ urine glowed, making it easy to detect and monitor over time through a simple urine test. This test could allow clinicians to accurately adjust the dose of immunosuppressants to control the immune response.

“Adjusting the dose is very difficult but very important because heavy immunosuppression increases occurrence of infections and patients who receive it also get cancer more often,” said Kwong.

Image: A T cell, here in violet, makes contact with a transplant organ cell, here in brown and purple. The T cell secretes the enzyme granzyme B, here in gray, which attacks the organ cell. But granzyme B also severs fluorescent signal molecules, in green, from the rejection detecting nanoparticle, in light red. The signal molecules makes their way into the urine, where they give off a fluorescent cue.

Study in Nature Biomedical Engineering: Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity…

Via: Georgia Tech…