Pint of Postdoc Speaker Recap - Dr. Laura Bracaglia

“Vascular Targeted Nanoparticles to prevent Immune Mediated Injury”

Dr. Laura Bracaglia

Edited by:

Jennifer Blackburn (assisted by Aileen Fernandez)

Abstract:

In solid organ transplantation, the host immune system acts to reject the transplanted graft. This process is facilitated at the graft endothelial surface, where inflamed endothelial cells (ECs) upregulate adhesion molecules and recruit effector cells of the host immune system. To combat this dysfunctional inflammation, anti-inflammatory agents can be administered directly to the graft endothelium. Laura Bracaglia and her colleagues have designed a strategy for local and sustained delivery of these agents using molecularly-targeted polymer nanoparticles (NPs) during a period of ex vivo normothermic machine perfusion (EVNMP) of the organ. 

For our November 2020 Pint of Postdoc series, she shared about her research which focuses on several approaches for therapeutic delivery using polymeric NPs as well as strategies to direct NPs using molecular targets to the endothelial cells of interest. With her lab, she has discovered that rapid accumulation of NPs on ECs relies on both the density and accessibility of the potential ligands, and that these parameters can be measured directly in the relevant human vessel setting. Further, through the sustained release of nucleic-acid or small molecules from novel polymeric systems to targeted endothelial cells in intact human vessels, the immune cell activation and propagation of several inflammatory pathways is reduced in those regions. The experiments conducted within these platforms are being used to develop a high throughput preclinical approach to optimize immune therapy for local and robust treatment in human organ transplant.