Anna Salvati, Groningen Research Institute of Pharmacy
Late News: Dissecting How Cells Internalize and Process Nano-Sized Drug Carriers for Nanomedicine Applications
Written by Jessalyn Hui Ying Low
For intracellular delivery of nanomedicines, nanomedicines have to first interact with the cell membrane and be recognized, after which they can be internalized by cells via a variety of cellular pathways. In this talk, Anna Salvati explains the research work done to understand deeper such interactions, in particularly how corona molecules can affect internalization of drugs. “By understanding these interactions better, we can design nanomedicines to achieve the desired outcomes at cell level and control these interactions,” says Salvati.
Salvati explains that when in a biological environment, formation of a corona occurs on the nanocarriers due to adsorption of surrounding biomolecules. This corona can in fact be recognized by cell receptors, mediating the interaction between the cells and nanoparticles. It was found that for the same nanoparticle, but with different corona compositions, the internalization pathway of the nanoparticle is also different, implying that different corona compositions are recognized differently by cell receptors. Salvati also highlights that even if a specific receptor is targeted, cells can internalize the nanoparticles via a different pathway as compared to the endogenous ligands. In addition, by changing the compositions of liposomes, it was shown how the corona composition can be tuned, and how this in turn affects the kinetics and mechanisms of uptake by the cell.
To understand better the mechanisms of internalization, it is also important to have better models beyond conventional in vitro cell cultures, as Salvati shares. One of such models the research group has developed are in vitro endothelial cell barriers, to mimic the barriers that nanomedicines face in vivo. It was found that when cells developed into a barrier, endocytic markers were expressed to different levels, and had a lower nanoparticle uptake as compared to standard cell cultures, indicating that such organization of the cells influences how nanoparticles are processed. Another model is a precision-cut tissue slices ex vivo model, where it was shown that precision-cut liver slices reproduced the preferential accumulation of nanoparticles by Kupffer cells as observed in vivo. This highlights how these models can be leveraged to better understand cellular internalization of nanomedicines occurring in vivo and optimize the design of nanomedicines.