by Paul Arnold, Phys.org
edited by Gaby Clark, reviewed by Robert Egan
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The role of capsules in organ-targeted delivery. Credit: Nature (2026). DOI: 10.1038/s41586-026-10158-7
In recent years, mRNA in lipid nanoparticles (mRNA–LNPs) has emerged as a promising strategy for treating numerous conditions, including COVID-19, various cancers and chronic genetic disorders. To date, this technology has not been successfully used for pancreatic diseases, but that could be about to change. In a paper published in Nature, scientists from China report the development of a new lipid nanoparticle drug-delivery system specifically designed for the pancreas.
Problem with the pancreas
Lipid nanoparticles are a special class of fat-based carriers that encapsulate and deliver nucleic acids such as messenger RNA into cells. Among the reasons they have not worked for the pancreas until now is that most LNPs naturally accumulate in the liver and spleen. That means the therapeutic molecules they carry can’t accumulate to high enough levels to be beneficial.
However, the research team realized that while the liver and spleen are wrapped in a dense, protective outer layer called a capsule, the pancreas is only covered by a thin layer of connective tissue. They wondered if these organ capsules act as a biological filter. If so, they could perhaps design nanoparticles large enough to be physically blocked by the walls of the spleen and liver, leaving the pancreas as the only place to go. They named this discovery the capsule-filter-mediated pancreatic-targeted (CAMP) mechanism.
video below at: https://phys.org/news/2026-02-size-shifting-nanoparticles-successfully-mrna.html?utm_source=nwletter&utm_medium=email&utm_campaign=daily-nwletter
Bright fluorescent boundaries were observed in the liver and spleen, indicating a membranous structure covering these organs, which were particularly pronounced for the large-sized (approximately 300 nm) group. Credit: Nature (2026). DOI: 10.1038/s41586-026-10158-7The researchers engineered several lipid nanoparticles of different sizes and tested them in mice. They found that small particles still ended up in the liver and spleen while medium ones primarily targeted the liver. However, larger 300-nanometer particles were blocked by the thick organ capsules but could easily pass into the unprotected pancreas.
Expanding nanoparticle
But there was a catch. A large particle is needed to bypass the liver, but if it stays too large, a cell has difficulty absorbing it. To solve this, the team designed a nanoparticle that starts small (around 100 nm). Once it is injected into the abdominal cavity, it interacts with local proteins and rapidly grows to over 300 nm. When that happens, it can filter out of the liver and spleen so it can reach the pancreas. Once there, it can enter pancreatic cells to deliver its mRNA instructions.
“We reveal that organ capsules function as a filter to block the entry of intraperitoneally administered nanoparticles with large sizes into most abdominal organs, thereby achieving pancreatic-targeted delivery,” wrote the scientists in their paper.
Treatments and tests
They tested two types of medicine. The first was CRISPR-Cas9 instructions to silence genes that cause the immune system to attack the pancreas. After a single treatment, it halted autoimmune destruction for over 180 days in mice. Secondly, they delivered IL-2 (interleukin-2), which boosts the body’s natural defenses. When combined with cancer vaccines or CAR T cell therapy, the treatment shrank some tumors and eradicated others.
Following successful safety tests in non-human primates, the researchers believe their technology is ready for human trials.
A News and Views article about the research was also published in Nature.
Written for you by our author Paul Arnold, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.
Publication details
Jiaqi Lei et al, Pancreatic-targeted lipid nanoparticles based on organ capsule filtration, Nature (2026). DOI: 10.1038/s41586-026-10158-7
Aviad Elisha et al, Lipid nanoparticles engineered to target therapeutic RNA to the pancreas, Nature (2026). DOI: 10.1038/d41586-026-00294-5
Journal information: Nature
Key concepts
plant and animal testingNanostructures
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