Scientists from the University of Nottingham's School of Pharmacy have developed a groundbreaking method for analyzing the structure of lipid nanoparticles (LNPs), potentially revolutionizing vaccine and drug delivery systems. The research team demonstrated a novel cryogenic mass spectrometry approach that reveals the layers and molecular orientation within these tiny particles, providing unprecedented structural insights.
The findings, published in Nature's Mass Spectrometry Method Development collection, represent a significant advancement in understanding the technology that powered the Moderna and Pfizer-BioNTech COVID-19 vaccines.
Revealing the Hidden Structure of Lipid Nanoparticles
The research team utilized Cryogenic Orbitrap™ secondary ion microscopy (Cryo-OrbiSIMS) to examine LNPs in their native state. This high-pressure freezing cryo-preparation facility maintains biological samples close to their natural condition, allowing researchers to observe the true structure of these complex delivery vehicles.
"Characterising the native surface of delicate hydrated pharmaceutical systems used in the body has been a significant challenge for some time," explained Professor Morgan Alexander, who led the research. "This cryogenic molecular surface and interfacial analysis advance makes this exciting possibility real."
The new method provides detailed insights into the relative positions of each component within LNPs, knowledge that could clarify their intricate behavior and contribute to designing formulations with enhanced bio-properties.
Implications for RNA Therapeutics
LNPs gained prominence during the COVID-19 pandemic but have broader applications in delivering therapeutic treatments. They are currently used in small interfering RNA-based drugs to treat rare hereditary diseases like polyneuropathy, developed by Alnylam Pharmaceuticals.
Dr. Robert Langer from Massachusetts Institute of Technology, a co-author on the research paper, highlighted the significance: "Effective drug delivery relies on an intricate mix of molecules in lipid nanoparticles to effectively deliver RNA therapeutics, but these can vary in efficacy and can be difficult to engineer. This research provides a new way of characterising and understanding the make-up of lipid nanoparticles which could pave the way for engineering more potent and targeted LNPs."
The potential applications extend to challenging areas like lung-targeted gene therapy, with LNPs showing promise for treating conditions including cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma.
Advancing Manufacturing and Clinical Translation
Beyond improving therapeutic design, the research findings could enhance quality control during manufacturing scale-up, facilitating the translation of LNPs from laboratory to clinical applications.
Kerry Benenato, Ph.D., Chief Platform Officer at Sail Biomedicines, which contributed to the research, emphasized the importance of understanding LNP surface structures: "The surface of lipid nanoparticles plays a critical role in shaping their behavior in the human body. By enabling precise surface characterization, the technology the team has developed paves the way for the engineering by design of LNP-based medicines with tunable properties, including biodistribution, thereby expanding the potential of RNA-based therapeutics."
The collaborative research effort included scientists from Sail Biomedicines, Massachusetts Institute of Technology, and the National Physical Laboratory in the UK, demonstrating the international interest in advancing this promising technology.
As RNA therapeutics continue to emerge as a powerful approach to treating previously untreatable conditions, this new analytical method provides researchers with critical tools to optimize delivery systems, potentially accelerating the development of more effective and targeted treatments for a wide range of diseases.
