Schematic of the preparation of TA/DMG-PEG micellar cubosomes using a NanoAssemblr microfluidic device. Credit: Advanced Materials (2025). DOI: 10.1002/adma.202505830
An Australian research team has achieved an advanced materials breakthrough that opens the door to a new generation of nanodrug applications. From drug delivery, to diagnostics, to gene editing and beyond, the breakthrough has the potential to improve outcomes for patients around the world in coming decades.
Using the Australian Synchrotron and state-of-the-art cryo-imaging, the team has developed a new class of lipid nanoparticles (LNPs) that form complex internal arrangements such as cubes or hexagons. These "nonlamellar" (cubes/hexagons) structures significantly expand the potential of LNPs by providing more surface area and greater versatility for carrying a wide variety of cargo, including small-molecule drugs, proteins, metal ions and mRNA.
LNPs are best known as the delivery vehicles that enabled the Pfizer–BioNTech and Moderna COVID-19 vaccines, protecting fragile mRNA molecules and ensuring they reach target cells. Their success during the pandemic sparked global investment in RNA medicines, which are now being explored for cancer treatment, immunotherapy and genetic disorders.
The study, published in the journal , was co-led by University of Melbourne Laureate Professor Frank Caruso, Head of the Caruso Nanoengineering Group, and Dr. Yi (David) Ju, Head of the Nanomedicine and Gene Therapeutics Laboratory at the Olivia Newton-John Cancer Research Institute (ONJCRI) and La Trobe University, together with colleagues from RMIT University.
"A key benefit of our new class of LNPs is that their nonlamellar structures are tuneable—meaning their internal order and size can be precisely adjusted by varying the formulation. This flexibility allows us to design delivery systems for different classes of therapeutic molecules," said first author of the study, Dr. Shiyao Li, who is a Postdoctoral Researcher at ONJCRI.
"This new class has been created from polyphenols—naturally occurring plant compounds with antioxidant and anti-inflammatory properties—in combination with a lipid," Professor Caruso said.
"The breakthrough will bring insights into nanostructured materials design and allow new applications in diverse fields, from molecular delivery for cancer treatments, to protein and gene therapies, and even diagnostic nanomaterials. There is wide capacity to tailor these materials to different delivery needs."
Dr. Ju said the team has patented a library of this new class of LNPs and that "the team is very excited about the potential of this new platform technology and is looking for industry partners to work with to develop new mRNA therapeutics."
"Within five years, we hope to validate the platform with new therapeutic applications in animal models. Importantly, these LNPs can be produced using the same assembling equipment as current vaccines, but with components that are significantly more affordable than those found in existing LNP drug delivery formulations," he said.
More information: Shiyao Li et al, Polyphenol‐Mediated Engineering of Lipid Nanoparticles With Crystalline Mesophases, Advanced Materials (2025).
Journal information: Advanced Materials
Provided by University of Melbourne