Utskrift från Malmö universitets webbplats www.mah.se

Lipid nanoparticles-protein interactions: How to tune the formulation and improve the therapeutic performance

Contact person: Federica Sebastiani
Responsible: Federica Sebastiani
Co-workers: Marité Cárdenas, Sebastian Björklund, Dainius Jakubauskas, Tautgirdas Ruzgas, Marianna Yanez Arteta and Lennart Lindfors
Partner: AstraZeneca AB
Funding: The Knowledge Foundation (KK-stiftelsen)
Timeframe: 2019-01-01 -- 2020-12-31
Forskningscentrum: Biofilms - Research Center for Biointerfaces
Faculty/Department: Faculty of Health and Society, The Department of Biomedical Science

Therapeutic treatments based on the production of proteins by delivering messenger RNA (mRNA) represent a promising approach to treat many diseases that currently lack other alternatives. However, one of the major challenges is to protect these macromolecules from enzymatic degradation and deliver them into the target cells. Lipid nanoparticles (LNPs) formed by a cationic ionizable lipid (CIL), DSPC, cholesterol (Chol) and a pegylated (PEG) lipid have been approved by FDA for delivery of small interference RNA (siRNA) for the treatment of peripheral nerve disease. There are still concerns, nevertheless, about the safety profile of these nanoparticles.

A good understanding of the physical and chemical characteristics of the LNPs under study is necessary to progress from pre-clinical testing. In addition, the bio-distribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNPs administration, such as proteins in the plasma. Therefore, it is also important to understand the relation between LNP physical chemical properties and their ability to collect proteins from the plasma.

A common component found in the “protein corona” of LNPs is Apolipoprotein E (ApoE), which is responsible for the transport of fats in the systemic circulation and it triggers the fat uptake by cell-rich in low-density lipoprotein (LDL) receptors. This recognition step is critical to control the LNP’s circulation time and thus its pharmacological efficiency.

This project aims to understand how LNP composition and structure contribute to the LNP’s protein binding capacity and to unravel how LNP are taken up by cells, which is key to design LNPs that can selectively target organs.

Senast uppdaterad av Magnus Jando