Shining new light on the heterogeneity and dynamics of individual nanomedicine particles in biological environments

The limited ability of relating the dynamics of physicochemical properties with biological function for individual lipid nanoparticles (LNPs) is a current obstacle for the development of using LNPs as nanomedicines.

This proposal aims at enable label-free quantification of the dynamics of individual LNPs in terms of size, mass, composition, and structure in unknown biological particle environments.

This will be done by combining multiwavelength interferometric scattering (iSCAT) microscopy and convex lens-induced confinement (CLiC), where fluorescence-based LNP characterisation using CLiC has been pioneered by the host Prof. Leslie at University of British Columbia.

This proposed project consists of three parts: (1) developing multiwavelength CLiC-iSCAT, (2) investigate dynamics of individual LNPs in controlled sample environments, and (3) measure the LNP dynamics inside live cells. Given the established CLiC protocols, iSCAT microscopes in Dr.

Leslie’s lab, and my experience of optics earned during my PhD project, step (1) is expected to take between 6-12 months, enabling 24 months to correlate LNP dynamics with biological function. To achieve the image analysis needed for this project, I will also work with the group of Prof. Giovanni Volpe at University of Gothenburg.

Overall, this project will push the frontiers of multiparametric characterisation of individual biological nanoparticle and provide new knowledge to aid the development of next-generation RNA–LNP therapies.