Article translated and adapted from English, originally published by the American headquarters of the Epoch Times.
A recent preprint paper from the University of Pennsylvania (UPenn) showed that lipid nanoparticles, which carry COVID-19 mRNA in vaccines, cause inflammation inside cells. However, this inflammation can be reduced if the appropriate lipid nanoparticle is used.
Researchers tested several different lipid nanoparticle formulations on animals, including ALC-0315 and SM-102, used in the Pfizer and Moderna vaccines, respectively.
They found that all lipid nanoparticles tested cause inflammation by damaging cellular components called endosomes. However, the degree of inflammation varies depending on the degree of damage.
Additionally, researchers found that a lipid nanoparticle called 4A3-SC8 induced a lower level of inflammation causing less damage. Inflammation could also be reduced with the drug thiodigalactoside, which prevents the cell from detecting serious damage.
Since the implementation of COVID-19 vaccines, lipid nanoparticles have become a popular technology within nanomedicine.
“Right now, the entire field of nanomedicine is focused on how to amplify LNP (lipid nanoparticle) formulation for all other diseases,” Wang Yufei, a postdoctoral researcher at UPenn and one of the study’s authors, told The Epoch Times .
“Our group and others have recently shown that LNPs can induce severe inflammation and worsen pre-existing markers of inflammation by up to >10-fold,” the researchers wrote in the preprint.
Although most people who have taken COVID-19 vaccines have not experienced serious adverse reactions, some studies suggested hyperinflammatory syndromes that occur after vaccination.
“One question is, how can we use LNPs in a safer and more efficient way? So that is one of the main goals that we try to optimize the LNP formulation and understand the mechanics of LNP interaction with the whole body,” said Ms. Wang.
Lipid Nanoparticles Drill Holes in Cellular Structures
The authors also explored how lipid nanoparticles cause inflammation when introduced into cells.
They exposed mice to different types of lipid nanoparticles—either by injection or inhalation—each carrying mRNA cargo. The animals were then examined 24 hours after exposure.
Normally, when cells accept a foreign substance, it is encapsulated in sacs known as endosomes. Inside the endosomes, the substance is digested and broken down to ensure that nothing harmful is introduced into the cell.
Lipid nanoparticles escape digestion by punching holes in endosomes.
Researchers found that the larger the hole, the greater the inflammation. Furthermore, those whose mRNA information is more expressed and amplified also tended to have more inflammation.
The 4A3-SC8 lipid nanoparticle punctured smaller holes, triggering a milder inflammatory response. Surprisingly, it also caused robust expression of the mRNA information it carried and was the only lipid formulation that did not align with the trends.
The authors also found that blocking galectins, proteins that detect large holes in endosomes, successfully reduced inflammation.
Empty lipid nanoparticles cause the most inflammation
The study also tested whether the internal mRNA cargo or the surrounding lipid nanoparticles caused more inflammation.
“In our paper, we prepared some LNPs without charge—that is, just the lipid,” said Ms. Wang. They also tested LNPs with polystyrene polymers.
“Empty LNPs lead to the highest cytokine concentrations,” the authors wrote.
Compared to immune cells exposed to particles carrying mRNA or polystyrene polymers, inflammation in animals exposed to empty lipid nanoparticles was 20 to 500 times greater, respectively.
Lipid nanoparticles reduced lung inflammation
Although lipid nanoparticles cause inflammation, the preprint also showed that lipid nanoparticles can benefit health in the right combinations.
The authors tested the 4A3-SC8 lipid nanoparticle with mRNA for the anti-inflammatory chemical thiodigalactoside in mice with lung injuries that mimicked acute respiratory distress syndrome. When the mice were examined hours later, inflammation was reduced.
Past UPenn work showed that lipid nanoparticles carrying modified RNA could exacerbate inflammatory conditions.
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Tags: Lipid nanoparticles COVID19 vaccines inflammation cells preprint study vaccines COVID19 nanoparticles lipid nanoparticles
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