University of Pittsburgh

PITTSBURGH, March 6, 2025 /PRNewswire/ -- Duquesne University's Nanomedicine Manufacturing Laboratory (NML) is taking tiny particles and using them to help remedy major health issues. The lab, led by Duquesne Associate Professor of Pharmaceutics Dr. Jelena Janjic, was the first to create pain nanomedicine for trauma and surgical pain, which could lead to reducing the use of opioids for recovery. The NML also developed the first oxygen carrier with imaging clinical grade agents for real-time tracking during organ/limb preservation, which may reduce organ rejection and lead to improving transplantation success. So it wasn't much of a surprise when the NML was tapped to participate with other institutions to make whole eye transplants a reality. More than 40 scientists, doctors and industry experts are joining together for the $56 million project from the Advanced Research Projects Agency for Health (ARPA-H) Transplantation of Human Eye Allografts (THEA) program. Jeffrey Goldberg, MD, PhD, Blumenkranz Smead professor and chair of ophthalmology at the Byers Eye Institute at Stanford, serves as the principal investigator. José-Alain Sahel, MD, professor and chair of the Department of Ophthalmology at the University of Pittsburgh, co-directs the initiative with Goldberg. "We are uniquely prepared to work in multiple task areas of this project," Janjic said, adding that Duquesne was the only partner in the project to receive two sub-proposer contracts. "The nanomedicines we create provide imaging of the tissue during rejection, and in response to immunosuppression treatment, image optic nerve neuroinflammation post repair, and importantly aid in organ preservation and offer drug delivery that assists in transplantation." These horizon-expanding opportunities are part of Duquesne's DNA, benefiting researchers, students and society by moving scientific discovery forward. A key part of the NML's success is its quality-by-design process, which allows it to produce cost-effective, robust and scalable manufacturing methods for nanomedicines with a high level of quality control. Typical nanotechnology-based therapeutics are often burdened with high costs and challenging quality control issues. NML is unique in its ability to produce multi-liter quantities of complex patent-protected nanomedicine formulations across multiple uses, from pain relief to organ preservation. The ARPA-H funding, which includes $1.2 million to Duquesne, is just the latest example of NML's success. Last year, the lab received a $1.5 million grant from the U.S. Department of Defense to expand research into using nanoparticle technology to preserve human limbs for transplantation surgeries. SOURCE Duquesne University WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Researchers have pioneered a new catalytic transformation that converts epoxides into fluorinated oxetanes, a coveted but difficult-to-make class of drug molecules that escaped synthetic preparation for years. By unlocking a pathway to these valuable drug scaffolds, this discovery potentially opens the door to new medicines for drug discovery applications. Researchers from the National University of Singapore (NUS) have pioneered a new catalytic transformation that converts epoxides into fluorinated oxetanes, a coveted but difficult-to-make class of drug molecules that escaped synthetic preparation for years. By unlocking a pathway to these valuable drug scaffolds, this discovery potentially opens the door to new medicines for drug discovery applications. The research team was led by Associate Professor Koh Ming Joo from the NUS Department of Chemistry, together with Professor Eric Chan from the NUS Department of Pharmacy and Pharmaceutical Sciences and Professor Liu Peng from the University of Pittsburgh, United States of America. The research breakthrough was published in the scientific journal Nature Chemistry on 20 February 2025. Four-membered heterocycles such as oxetanes and β-lactones are common motifs in natural products and pharmaceuticals, with numerous examples documented in both synthetic and biological studies. The introduction of fluorine into organic molecules often imparts desirable attributes, which has contributed to successful outcomes in drug discovery. In this vein, isosteric replacement of a CH2 unit within an oxetane (or C=O group within a β-lactone) with CF2 results in α,α-difluoro-oxetanes, a prized class of heterocyclic compounds with combined attributes of small-ring heterocycles and fluorine. While these fluorinated oxetanes hold great promise as lead compounds for further development into new medicines, their synthetic preparation has largely eluded chemists. Assoc Prof Koh said, "Traditional ways of constructing the oxetane ring cannot directly produce α,α-difluoro-oxetanes, owing to a lack of suitable fluorine-containing precursors or reagents, or both. Furthermore, traditional chemistry often leads to complications such as ring rupture, defluorination and other undesired side reactions. A new synthetic approach was clearly needed." A novel method to synthesise fluorinated oxetanes The researchers deviated from the standard logic of synthesis by designing a new strategy that inserts a difluorocarbene species selectively into the structure of readily available three-membered epoxides. This process is facilitated by an inexpensive copper catalyst, which stabilises the difluorocarbene generated from a commercially available organofluorine precursor. The resulting copper difluorocarbenoid complex coordinates with the epoxide and triggers site-selective ring cleavage and cyclisation, to yield the desired α,α-difluoro-oxetane product via a metallacycle intermediate. Computational studies by Prof Liu's group provided insight into the new reactivity mode and its underlying mechanism. Additionally, lipophilicity and metabolic stability studies performed by Prof Chan's team supported the potential of these fluorinated oxetanes as valuable drug scaffolds. To demonstrate the practical utility of their method, the researchers successfully synthesised fluorine-containing analogues of oxetane, β-lactone and carbonyl pharmacophores commonly found in a variety of biologically active compounds. Computed electrostatic potential maps of isosteric oxetane, α,α-difluoro-oxetane and β-lactone further indicated the potential of these compounds to serve as analogues of each other. "By inventing a reliable route to fluorine-containing oxetanes, we can now incorporate these motifs into the design of novel small-molecule therapeutics. This opens up exciting opportunities to develop new medicines that could potentially treat previously incurable diseases," added Assoc Prof Koh. Studies are ongoing to investigate the biological properties of these newly synthesised drug analogues and extend the methodology to other classes of heterocyclic drug-like compounds.

FRIDAY, Feb. 14, 2025 – Kidney transplants can be lifesaving, but a new study suggests that some recipients may be at greater risk for a rare and aggressive cancer known as post-transplant lymphoproliferative disorder (PTLD). The culprit is the Epstein-Barr virus (EBV). Best known for causing mononucleosis, Epstein-Barr virus is also linked to risk for several cancers, including PTLD. More than 90% of adults in the U.S. are or have been infected with EBV. When kidney transplant patients who’ve never been exposed to it receive organs from a donor who has carried the virus, they can develop PTLD. For the study, researchers analyzed data from two large U.S. transplant centers. They compared rates of EBV among kidney transplant recipients whose donors tested positive for the virus. Fully 22% of never-infected transplant recipients who received a kidney from a donor who had been infected with the virus developed PTLD within three years after their transplant. Nearly one-third of those affected by PTLD died from it during the study period. People who receive kidney transplants must take immunosuppressive medications to prevent their body from rejecting the new kidney. These medications increase the risk of developing EBV-associated PTLD, according to the National Kidney Foundation. The new data suggest that up to 5% of adult kidney transplants -- as many as 1,200 patients per year -- could be at risk for PTLD. This is five to 10 times higher than previously estimated based on national registry data, the study authors point out. “National registry data likely underestimates PTLD incidence due to incomplete reporting and errors in tracking whether organ donors and recipients have been exposed to viruses like EBV,” said study author Dr. Vishnu Potluri in a news release. Potluri is an assistant professor in the Renal Electrolyte and Hypertension Division at the Hospital of the University of Pennsylvania in Philadelphia. The risk of being diagnosed with PTLD after a kidney transplant is widely recognized, but until now, it has mainly been studied in children who are less likely to have been exposed to EBV. “Given the significant threat to survival posed by PTLD and the substantial discrepancy between our findings and prior data, our study serves as a call to action to prioritize further research to enhance the safety and survival of this vulnerable transplant population,” said study author Dr. Chethan Puttarajappa , an associate professor in the renal-electrolyte division at the University of Pittsburgh. The findings suggest it is time to change how kidney transplant patients are monitored for EBV and PTLD. “We need to rethink how we monitor patients for EBV infection and how we manage immunosuppression for these high-risk patients,” said Dr. Emily Blumberg , director of Transplant Infectious Diseases at Penn Medicine. "This includes early and routine testing for EBV and exploring personalized adjustments to immunosuppressive therapy." EBV screening rates vary among centers in the U.S., and many do not routinely screen for EBV after kidney transplantation. If a patient develops PTLD, lowering doses of immunosuppressive drugs is the first step, according to the National Kidney Foundation. The study was recently published in the Annals of Internal Medicine . Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.