The findings suggest the potential to accelerate the development of RNA-based medicines.
New research suggests reducing the amount of cargo in lipids nanoparticles (LNP) may improve drug efficiency.
This is remarkable, given that LNPs typically have 1 to 5 percent of their cargo released inside the cells, and have a “low efficiency limit,” according to Artu Breuer, a researcher at the University of Copenhagen.
“For example, in cancer treatments where cells are rapidly dividing, if you deliver too little RNA, the cells will outpace the treatment.”
To overcome this challenge, Breuer Others. We have developed a high-throughput single nanoparticle measurement tool that can provide a more effective development method. RNA-based medicine.
Instead of looking at the average properties of a batch, the team measured both the size of each particle and the amount of cargo it contained.
[the researchers found] Two distinct subpopulations: organized particles, where the cargo is well structured, and amorphous particles, which are less organized. What surprised me was that the messier stuff actually worked better inside the cells. ”
“Instead of assuming all nanoparticles within a batch are the same, we found that there was a huge amount of variation,” Breuer explained.
Importantly, the researchers discovered “two distinct subpopulations: organized particles, whose cargo is well-structured, and amorphous particles, which are more disordered. Surprisingly, the disordered particles actually function better inside cells.”
“In organized nanoparticles, positively charged lipids are tightly bound to negatively charged RNA,” Breuer said.
“When particles enter a cell, their attractive forces hold everything together, even if conditions change. But in unorganized particles, there is some separation between the charges. When conditions inside the cell change, the positive charges repel each other, causing the particles to break apart and the drug to be released.”
This goes against the traditional drug discovery This process ensures that each nanoparticle is loaded with as much drug as possible as efficiently as possible.
Organized lipid nanoparticles with well-structured cargo (right) and amorphous lipid nanoparticles with more disordered cargo (left). Credit: Artu Breuer, University of Copenhagen.
This finding suggests that rather than maximizing the amount of cargo carried by each particle, it is better to establish an unorganized internal structure so that the LNP cargo can be released once at its destination.
However, Professor Breuer cautioned that this does not mean leaving nanoparticles empty, but should encourage research avenues that focus on “loading them with enough RNA while maintaining a more effective disordered structure within the cell.”
Screening of LNPs formulation Using this method helps researchers understand which structural features are important. delivery.
This study 2026 Biophysical Society Annual Meeting.