Innovative Lipid Nanoparticle Shapes Enhance mRNA Drug Delivery Efficiency

Researchers from RMIT University and Osaka University have made a significant breakthrough in the field of nanomedicine by discovering that the internal shapes of lipid nanoparticles play a crucial role in their absorption by human cells. This innovative study, published in the June 2025 issue of the journal *Small*, demonstrates that certain lipid nanoparticle configurations can be absorbed up to eight times more effectively than traditional forms, which could revolutionize vaccine and drug delivery methods.

Lipid nanoparticles have gained prominence as essential vehicles for drug and gene delivery, particularly highlighted by the success of mRNA vaccines during the COVID-19 pandemic. Despite this success, the science behind efficiently delivering these therapies to target cells remains underdeveloped. According to Sue Lyn Yap, the study's lead author and a PhD candidate at RMIT University, "One of the major challenges in nanomedicine is that most nanoparticles are taken up by cells through pathways that trap and degrade them, with studies showing less than 2% of gene therapies successfully reach their target inside the cell."

The research highlights the differences in internal structures of lipid nanoparticles, specifically focusing on cubosomes—complex three-dimensional cubic shapes formed from lipid self-assembly in water. The findings reveal that cubosomes significantly outperform liposomes, the conventional structure used in many current lipid-based nanomedicines. Yap noted, "In vitro tests using an epithelial cell line found cubosomes were the most efficient at entering cells, being eight times more likely to do so compared to liposomes."

The study also uncovers that cubosomes can penetrate cells through more passive routes, such as direct fusion with the cell membrane, bypassing the typical cellular barriers that lead to degradation. This characteristic could be a game changer in the design and application of lipid nanoparticles moving forward.

The collaborative effort included distinguished researchers such as Professor Calum Drummond AO, Professor Charlotte Conn, and Dr. Nhiem Tran from RMIT, alongside their counterparts at Osaka University. This partnership facilitated a comprehensive examination involving multiple facilities, including the Australian Synchrotron (ANSTO) and the RMIT Micro Nano Research Facility (MNRF).

As the research progresses, the team aims to explore how these structured nanoparticles perform within the human body and whether they can be tailored for targeted delivery to specific tissues or diseases. Dr. Tran emphasized the importance of this work, stating, "Our next steps will involve investigating how these innovative nanoparticles can enhance therapeutic targeting and efficacy in clinical applications."

In sum, the discovery of how specific shapes of lipid nanoparticles can enhance cellular absorption offers promising potential for advancing mRNA gene therapy and other medical treatments. With further research, these findings may lead to more effective and efficient methods for delivering crucial therapies, ultimately improving patient outcomes and expanding the horizons of nanomedicine.