Register for the upcoming Teatime Webinar

 

Please fill out this form to register for the upcoming PNI Teatime Webinar Series: Endosomal escape of Lipid Nanoparticles: novel insights using reflectivity techniques, presented by Dr. Alice Spadea,  Postdoctoral Researcher at the University of Manchester.

 

Date: Wednesday, September 21

Time: 2:30pm GMT+1 | 3:30pm CEST

 

 

Abstract

Efficient endosomal escape represents a major bottleneck in the drive to improve the efficacy of lipid nanoparticles by increasing the amount of nucleic acid cargo delivered to the cytosol. Once in the acidic conditions of the endosome, the LNPs become positively charged and (some of) their constituent molecules partition into the endosomal membrane, probably forming hexagonal structures, which disrupt the membrane allowing the release of the LNPs nucleic acid cargo into the cytosol. Despite models of the mechanism of interaction being proposed, an effective in vitro assay to study the fate of the LNPs in the endosome is an unmet need. Here, surface pressure (π) and ellipsometry (Δint) data have been used to obtain, for the first time, novel insight into the interaction between LNPs and model endosomal monolayers, highlighting the different types of processes occurring at the air/water interface, such as insertion of lipids, binding of whole LNPs and ionizable lipid-nucleic acid complexes delivery. Such new information represents the basis for future studies on different LNPs formulations and can be used to design delivery systems with optimised nucleic acid delivery capacity.