A groundbreaking development in mRNA delivery techniques has emerged from researchers at the University of Nevada, Las Vegas (UNLV), promising to transform treatments for diseases related to the pancreas, including both diabetes and pancreatic cancer. This pioneering study, recently published in the prestigious journal Advanced Materials, introduces an innovative approach that exploits the body’s intrinsic biological pathways to achieve targeted delivery of mRNA therapeutics specifically to the pancreas. Such precision offers new hope for therapies that require an unprecedented level of organ specificity without the systemic side effects of conventional treatments.
The challenge with existing intravenous mRNA delivery systems has long been their inability to selectively localize therapeutic agents to the pancreas. Most current methods rely on systemic circulation that tends to scatter administered drugs widely throughout various tissues, diminishing efficacy and increasing unwanted off-target effects. The research team at UNLV, led by Professor Chandrabali Bhattacharya, successfully circumvented this limitation by engineering a novel class of lipid nanoparticles, which they have trademarked as ENDO (Endogenous Targeting Lipid Nanoparticles). Unlike conventional nanoparticles that follow non-specific biodistribution patterns, ENDO particles harness the body’s endogenous material transport mechanisms to home in on the pancreas with remarkable specificity.
A key insight driving this technology is the exploitation of Vitamin D receptors found on the surface of certain cells. These receptors, though distributed widely in the body, are present in particular conformation and density on pancreatic cells’ surfaces, making them ideal “coordinates” for nanoparticle targeting. By incorporating vitamin D or similar biologically relevant molecules into the lipid nanoparticle formulation, the research team was able to program these particles to interact selectively with Vitamin D receptors, effectively commandeering the body’s natural transport pathways to direct their cargoes to the pancreas.
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This targeted delivery system was shown to achieve a phenomenal selectivity rate of approximately 99 percent for the pancreas following systemic intravenous injection. To put this achievement into perspective, no previous material or delivery vector had demonstrated such a high degree of natural pancreatic tropism upon intravenous administration, marking a decisive milestone in nanomedicine. This breakthrough is not merely a proof-of-concept but represents a scalable and adaptable platform for the systemic administration of nucleic acid-based therapies to an organ notoriously difficult to reach.
The implications of this targeted mRNA delivery technology are immense, particularly for chronic and life-altering conditions such as diabetes. Current insulin therapies require lifelong administration and continuous monitoring, often burdening patients with recurrent costs and variability in glucose control. mRNA therapeutics delivered directly to pancreatic cells could potentially modulate or restore endogenous insulin production, thereby mitigating disease progression. Lead author Ivan Isaac emphasizes that this innovative therapy could slow down or even reverse beta cell loss—the hallmark of diabetes progression—reducing the need for frequent injections and offering patients a significantly improved quality of life.
Beyond diabetes, the ENDO platform holds promise in addressing pancreatic cancer, a disease with notoriously poor prognosis and limited treatment options due to the pancreas’ relative inaccessibility. By enabling precise delivery of mRNA molecules encoding for tumor suppressors or immune modulators, this technology could revolutionize how oncologists approach pancreatic tumors, potentially enhancing therapeutic efficacy while minimizing systemic toxicities associated with chemotherapy or radiation.
The researchers achieved this feat by meticulous reengineering of the lipid nanoparticle composition. Incorporating endogenous molecules such as vitamin D not only improved targeting specificity but also improved biocompatibility and reduced immunogenicity. This endogenous biomimicry enables the nanoparticles to evade rapid clearance by the immune system, prolonging their circulation time and enhancing tissue uptake. Through extensive in vitro and in vivo studies, the team demonstrated the critical role of the Vitamin D receptor-mediated route, confirming that blocking these receptors significantly reduces pancreatic nanoparticle uptake, thereby validating the targeting mechanism.
This accomplishment also marks a critical conceptual advancement by breaking the existing paradigm that liver-targeted delivery is often the default in 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 paves the way for expanding mRNA therapeutics beyond hepatic applications to other vital organs that have remained elusive targets until now.
UNLV’s study further underlines the versatile nature of the ENDO system, which the researchers are already customizing for delivery to other challenging tissues such as the brain and heart. These organs similarly pose formidable barriers for drug delivery due to protective anatomical features like the blood-brain barrier and complex vascularization. The researchers believe that by adjusting ligand composition and nanoparticle architecture, this platform could eventually offer unprecedented precision in treating neurodegenerative disorders, cardiovascular diseases, and beyond.
Ivan Isaac, a graduate researcher deeply involved in the development of ENDO, envisions a future where precision nanomedicine fundamentally reshapes therapeutic regimens. Emphasizing safety and patient tolerance, he expects next-generation delivery platforms to reduce immune activation and side effects often associated with RNA vaccines and therapies, thereby broadening the clinical applicability of mRNA technologies. This could herald a new era where treatment regimens become less frequent, less invasive, and more effective.
Commercialization efforts are underway in collaboration with UNLV’s Office of Economic Development, reflecting confidence in the technology’s translational potential. The ability to reliably produce and scale ENDO nanoparticles could prompt rapid adoption in pharmaceutical pipelines, encouraging partnerships aimed at accelerating clinical trials and eventual FDA approval. The team remains committed to advancing this platform from bench to bedside, anticipating that their innovation will serve as a foundational blueprint for precision organ-targeted therapeutics.
Professor Bhattacharya underscores the monumental nature of this achievement, framing it as a foundational stepping stone that can catalyze a paradigm shift in drug delivery science. By bridging molecular biology, chemistry, and nanotechnology, the ENDO system exemplifies the convergence of interdisciplinary research driving forward the future of personalized medicine. The prospect of safer, more effective, and organ-specific therapies no longer seems distant but imminently achievable.
In conclusion, this transformative research signifies a remarkable stride toward overcoming one of the most persistent challenges in drug delivery — the ability to selectively and systemically target therapeutics to specific internal organs. The successful routing of mRNA to the pancreas via endogenous Vitamin D receptor pathways heralds a new dawn in the treatment of pancreatic diseases and opens vast unexplored avenues for mRNA-based interventions that could impact a plethora of medical conditions in the years ahead.
Subject of Research: Cells
Article Title: Reengineering Endogenous Targeting Lipid Nanoparticles (ENDO) for Systemic Delivery of mRNA to Pancreas
News Publication Date: 12-Jun-2025
Web References: https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202507657
References: Bhattacharya, C., Isaac, I., Patel, L., Tran, N., Singam, A., Yun, D.S., Guha, P., Park, S. (2025). Reengineering Endogenous Targeting Lipid Nanoparticles (ENDO) for Systemic Delivery of mRNA to Pancreas. Advanced Materials.
Keywords: Autoimmune disorders, Type 1 diabetes, Type 2 diabetes, Insulin, Diabetes, Diseases and disorders, Pancreatic cancer, Pancreatitis
Tags: advanced materials in medicinebreakthroughs in drug delivery researchdiabetes treatment innovationsendogenous targeting mechanismslipid nanoparticles for drug deliverymRNA delivery techniquesorgan-specific drug delivery systemspancreatic cancer therapeuticsreducing systemic side effects in therapiesselective localization of therapeutic agentstargeted therapy for pancreatic diseasesUniversity of Nevada research advancements
