Speaker
Description
Lipid nanoparticles (LNPs) as the carrier systems of pharmacologically active compounds have entered the spotlight during the Covid19 pandemics in the mRNA containing vaccines. However, the technology of nanoparticle drug delivery has been also studied as a tool for cancer or rare disease therapy. The advantage of LNPs comprised of ionizable lipids (ILs) is in the tunability of the IL properties to achieve optimal properties and support the targeted delivery into the organ of choice.
On its way from entering the body to releasing its cargo in the targed cell, the LNP has to move across the cell membrane - either by interacting with it directly, or via endocytosis. During this process, it inevitably encounters and interacts with lipids forming these membranes. This if however challenging to study experimentally.
To understand the molecular details of these interactions, a series of molecular dynamics simulation was created, to observe the effect of each natural membrane lipid separately. In a combination of free and biased simulations, the merging of the LNP with membrane lipids with different headgroups does indeed differ, largely based on the charge of the headgoup. As the ionizability is a key feature of the ILs, these findings are both in line with expectation, and provide a molecular resolution to the LNP-membrane fusion process.
