Researchers at the University of Nevada, Las Vegas (UNLV) have achieved a breakthrough in organ-specific drug delivery by developing the first intravenous material capable of targeting the pancreas with 99% selectivity. The innovation, published in Advanced Materials, introduces a novel platform called ENDO (Endogenous Targeting Lipid Nanoparticles) that could transform treatments for pancreatic diseases including diabetes and cancer.
"Until today, there has been no material that can be injected intravenously that automatically goes to the pancreas with 99% selectivity, an organ previously inaccessible to intravenous treatment," said UNLV biochemistry professor and research lead Chandrabali Bhattacharya. "This discovery is a first."
Revolutionary Targeting Mechanism
The ENDO platform exploits the body's endogenous pathways by utilizing Vitamin D receptors found on pancreatic cell surfaces. While these receptors are distributed throughout the body, they exist in particular conformation and density on pancreatic cells, making them ideal targeting coordinates for nanoparticle delivery.
"We wanted to see how endogenous material, such as Vitamin D, would change the nanoparticles carrying mRNA and interact with the body's pathways," explained Bhattacharya. "These systems can take the particles to different places in the body, and after testing a particular composition of material, we found that it's routing to the pancreas."
The team discovered that Vitamin D receptors serve as the delivery driver for the nanoparticles. By incorporating vitamin D or similar biologically relevant molecules into the lipid nanoparticle formulation, researchers programmed these particles to interact selectively with Vitamin D receptors, effectively commandeering natural transport pathways to direct therapeutic cargo to the pancreas.
Clinical Applications and Advantages
Current medication options target cell receptors throughout the body rather than specific organs, meaning very small amounts of administered drugs reach desired locations. The ENDO system's pinpoint delivery significantly reduces the likelihood of immune responses and side effects while requiring lower drug doses.
For diabetes treatment, the implications are particularly significant. "Traditional insulin therapy requires lifelong management with recurring expenses," said Ivan Isaac, a UNLV graduate researcher and first author on the study. "In contrast, mRNA therapies could slow down the loss of insulin, possibly reducing or reversing the disease condition with fewer routine injections."
The technology could enable mRNA therapeutics to modulate or restore endogenous insulin production by delivering therapeutic molecules directly to pancreatic cells. This approach could potentially slow down or reverse beta cell loss—the hallmark of diabetes progression—offering patients significantly improved quality of life with reduced injection frequency.
Expanding Beyond Liver-Targeted Delivery
The breakthrough represents a critical conceptual advancement by breaking the existing paradigm where liver-targeted delivery dominates mRNA therapies due to the organ's natural propensity to sequester nanoparticles. By devising a strategy to bypass the liver and enrich therapeutic payloads in the pancreas, the research opens pathways for expanding mRNA therapeutics beyond hepatic applications.
"One of the most exciting aspects of this research is its ability to push mRNA therapeutics beyond the liver, expanding treatment options for diseases that haven't been easily addressed with current delivery technologies," said Isaac.
The ENDO system's endogenous biomimicry enables nanoparticles to evade rapid immune system clearance, prolonging circulation time and enhancing tissue uptake. Through extensive studies, the team validated the targeting mechanism by demonstrating that blocking Vitamin D receptors significantly reduces pancreatic nanoparticle uptake.
Future Applications and Commercialization
The researchers are already pursuing further advancements in organ-specific drug delivery to other challenging targets including the brain and heart. These organs pose formidable barriers due to protective anatomical features like the blood-brain barrier and complex vascularization patterns.
Isaac, who plans to continue working in biopharmaceuticals creating next-generation drug delivery platforms, envisions broader applications: "I hope this work inspires further efforts in precision nanomedicine, where we can improve the safety of our treatments and enhance our tolerance for them."
Both Bhattacharya and Isaac are currently working with UNLV's Office of Economic Development to commercialize the findings. The ability to reliably produce and scale ENDO nanoparticles could prompt rapid adoption in pharmaceutical pipelines and encourage partnerships aimed at accelerating clinical trials.
"It is a colossal stepping stone and foundational block for so much more," said Bhattacharya. "This research has given us a blueprint for the future of medicine."
The successful routing of mRNA to the pancreas via endogenous Vitamin D receptor pathways represents a transformative stride toward overcoming persistent challenges in drug delivery, opening vast unexplored avenues for mRNA-based interventions across multiple medical conditions.
