Dissecting how cells internalize and process nano-sized drug carriers for nanomedicine applications

Anna Salvati / University of Groningen, Netherlands

July 13, 2023, 3 - 4 pm CEST

Online live talk



Nano-sized materials are used in nanomedicine to deliver drugs more efficiently to their site of action. In order to improve their efficacy, a better understanding of how cells interact with nano-sized materials is required. Our research is focused on characterizing the molecular details of the early interactions of nano-sized materials at the cell membrane, and the subsequent mechanisms of uptake and intracellular trafficking. To this end, we combine classic transport studies with inhibitors and RNA interference to genetic screening and proteomic-based methods to characterize the mechanisms by which nanoparticles are internalized by cells. Additional efforts are focused on developing advanced in vitro models more closely resembling the in vivo environment for our studies, including endothelial cell barriers and precision cut tissue slices from different organs.

We show that the molecules adsorbing on the nanoparticle surface once applied in serum (forming the nanoparticle corona) can interact with specific cell receptors and can affect the mechanism cells use for their internalization. Thus, using liposomes of different composition, the corona can be tuned to modulate uptake efficiency and uptake kinetics. By correlating corona composition and cell uptake efficiency, corona proteins promoting or reducing uptake can be discovered. Alternatively, we used reversible biotinylation of cell membrane proteins in live cells to directly identify nanoparticle receptors. We found that even when interacting with specific receptors, nanoparticles can be internalized by cells via different mechanisms than what it is usually observed for their endogenous ligands. For instance, nanoparticles interacting with the LDL receptor (LDLR) via their corona are internalized by cells via a mechanism that is not clathrin-mediated.9 Instead, we found that nanoparticle uptake is mediated by specialized curvature-sensing proteins, which may trigger alternative uptake mechanisms. Using nanoparticle of different properties, we show how their involvement varies depending on nanoparticle curvature and nanoparticle rigidity.

Our findings highlight the importance of understanding how cells interact with and process nano-sized materials in order to improve nanomedicine design.

Anna Salvati

graduated in Biological Sciences at the University of Florence, Italy, and in 2007 obtained a PhD in Chemical Sciences from the same University with a project focused on the preparation and physico-chemical characterization of drug carriers. She then joined the Centre for BioNano Interactions, University College Dublin, Ireland, where she focused on the development of methodologies to obtain reproducible quantitative data on nanoparticle uptake and interactions with cells.

In 2014, she has been awarded a Rosalind Franklin Fellowship from the University of Groningen (RUG), where she moved as an Assistant Professor to establish her group at the Groningen Research Institute of Pharmacy (GRIP). Since 2019 she is an Associate Professor in Nanomedicine. Her research is focused on understanding how nanomedicine interact with and are processed by cells. She also focuses on the development of novel methods to study these interactions and the optimization of advanced in vitro models for her studies. Her research has resulted in more than 90 papers which attracted >11k citations. Since 2020 she is an Associated Editor of the Beilsted Journal of Nanotechnology.