Researchers Find Disorganized Lipid Nanoparticles May Deliver Drugs More Effectively

New single-particle analysis reveals that less structured drug carriers could improve delivery of RNA-based therapies.

Feb. 22, 2026 at 12:17am

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Researchers have discovered that lipid nanoparticles (LNPs), the microscopic fat bubbles that delivered COVID-19 mRNA vaccines, may work better at releasing their cargo inside cells when they have a more disorganized internal structure, rather than being tightly packed. Using a new high-throughput method to analyze individual nanoparticles, the team found that highly organized LNPs with structured cargo may actually resist releasing their contents, while more amorphous particles can more easily fall apart and deliver the medicine once inside cells.

Why it matters

This finding challenges the conventional wisdom in drug delivery, where developers have focused on maximizing the amount of cargo in each nanoparticle and packing it as efficiently as possible. The new research suggests that maintaining a disorganized internal structure could be key to improving the low delivery efficiency of LNPs, which currently limits their use for treatments like cancer therapy where higher doses of RNA are needed.

The details

Artu Breuer and colleagues at the University of Copenhagen developed a new high-throughput method to measure individual lipid nanoparticles, rather than just looking at average properties of a batch. They found that highly organized LNPs, structured like the layers of an onion, may resist releasing their cargo once inside cells, as the positively charged lipids are tightly bound to the negatively charged RNA. In contrast, the more disorganized particles can more easily fall apart when conditions change inside the cell, allowing the medicine to be released.

  • The research will be presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21–25, 2026.

The players

Artu Breuer

A researcher at the University of Copenhagen who developed a new method to analyze individual lipid nanoparticles.

University of Copenhagen

The institution where Breuer conducts his research on improving the delivery efficiency of lipid nanoparticles.

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What they’re saying

“This low efficiency limits what we can do with LNPs as therapeutics. For example, in cancer treatment where cells are dividing rapidly, if you deliver too little RNA, the cells outpace the therapy.”

— Artu Breuer, Researcher

“Instead of assuming that every nanoparticle in a batch is the same, we found enormous variation, and we discovered two distinct subpopulations: organized particles where the cargo is neatly structured, and amorphous particles where it's more disorganized. The surprise was that the messy ones actually work better inside cells.”

— Artu Breuer, Researcher

What’s next

The researchers' new single-nanoparticle measurement tool gives them a way to screen LNP formulations and understand which structural features actually matter for delivery, potentially accelerating the development of more effective RNA-based medicines.

The takeaway

This research suggests a paradigm shift in how scientists design drug delivery vehicles like lipid nanoparticles. Rather than maximizing the cargo load in each particle, the focus may need to be on maintaining a disorganized internal structure that allows the medicine to more easily escape once inside cells, potentially improving the low delivery efficiency that has limited the use of LNPs for treatments like cancer therapy.