Rutgers scientists discover first lipid vascular ‘zip code’ within the lungs

Researchers at Rutgers Cancer Institute of Latest Jersey and Rutgers Latest Jersey Medical School (NJMS), along with other collaborating groups, have discovered the primary lipid vascular ‘ZIP code’ within the lungs. Getting a drug to where it is required within the human body is critical for successfully treating diseases including cancer and avoiding toxic side-effects, nevertheless it stays a significant challenge. One creative option has been to discover the unique protein receptors which are present on the surface of blood vessels at specific sites within the body that act like vascular ZIP codes. These ZIP codes may be physically paired with a ligand equivalent to a small protein or antibody that may be harnessed to guide and deliver a package equivalent to a drug or a diagnostic imaging agent to their specific molecular addresses. A few of these ligand-receptor pairs are already undergoing testing in clinical trials with anti-cancer and anti-obesity drugs.

Prior to the researcher’s findings, all vascular ZIP codes have been proteins. Their discovery uncovers a previously unrecognized lipid network of ZIP codes in blood vessels and opens up a brand new world of possibilities for improved diagnostics and coverings, including patients with severe human respiratory diseases equivalent to emphysema, COVID-19, COPD and lung cancer.

In 2008, the researchers discovered a ligand peptide that certain to the surface of lung vascular endothelial cells and will deliver a cell death notice on to the lungs in mice. Nonetheless, their usual biochemical and genetic methods didn’t discover the corresponding lung vascular ZIP code that the ligand was binding to.

The issue was that we had been searching for a protein. Our long series of frustrating failures led us to contemplate that the elusive goal is perhaps one other style of molecule, perhaps a lipid; that was a eureka moment.”

Wadih Arap, MD, PhD, director of Rutgers Cancer Institute at University Hospital Newark, professor and chief of the Division of Hematology/Oncology, Department of Medicine, Rutgers NJMS and a co-lead creator

The lipid ZIP code that they found on lung blood vessels known as C16-ceramide (also referred to as palmitoyl ceramide). It belongs to a family of closely related lipid molecules that perform many necessary cellular functions. These include helping viruses like Ebola and SARS-CoV-2 get into cells, and in addition triggering cell death. Increased levels of ceramides have long been known to be related to many lung diseases. Thus, C16-ceramide represents an unexplored avenue for many alternative diagnostic or therapeutic applications. As Renata Pasqualini, PhD, a resident member of Rutgers Cancer Institute and chief of the Division of Cancer Biology, Department of Radiation Oncology at NJMS one other co-lead creator remarked, “imaging plays such a necessary role in evaluating the lungs-;each, anatomically and functionally-;that we felt it was a possibility to make a clinical difference. Whether it’s for pulmonary screening, establishing a diagnosis, or monitoring disease severity, our approach and findings will hopefully represent an advance on this area.”

To solidify their discovery of a brand new lipid vascular ZIP code and ligand pair, they tested their hypothesis in genetically engineered ceramide-deficient mice and showed that the ligand was not capable of goal the lungs. To start to display what this might mean for patients, they tested two candidate medical applications. First, they showed that it could potentially be used for early diagnosis and monitoring of certain lung diseases by attaching the ligand to gold nanoparticles, which specifically lit up the lungs by utilizing optical and molecular imaging techniques. Finally, given the continuing COVID-19 pandemic, they showed that the ligand could also deliver a novel vaccine on to the lungs and stimulate a neighborhood immune response, which could possibly be more protective than currently existing vaccines which are injected into the arm.

Daniela Staquicini, PhD, resident member of Rutgers Cancer Institute and assistant professor of the Division of Cancer Biology, Department of Radiation Oncology at Rutgers NJMS said, “this body of labor actually encompasses an ensemble of three recently published manuscripts-;including this one-;on targeting different ZIP codes within the lung for multiple potential applications including non-invasive imaging and vaccine delivery, by which I had the privilege to function a co-first-author on behalf of several large teams of investigators.”

Next, the team plans to concentrate on discovering more lipid vascular ZIP codes within the blood vessels that serve other organs and particularly tumors as a option to higher goal anti-cancer drugs and can work to further translate these discoveries into true clinical applications for patients.