Description:

The Simpson Querrey Institute for BioNanotechnology (SQI) presents:

Vladimir R. Muzykantov, MD, PhD

Professor of Pharmacology and Medicine

Director, Center for Targeted Therapeutics & Translational Nanomedicine (CT3N)

Leader, Targeting Core & Research Theme, PENN Institute for RNA Innovation

The Perelman School of Medicine, University of Pennsylvania

"Targeted Delivery of Pharmacological Agents in the Vascular System"

Realizing the magnificent potential of biologicals requires targeted delivery to the desirable sub-cellular compartments in the cells of interest. To achieve this goal, we and other labs devise drug delivery systems (DDSs), including artificial systems such as liposomes and nanoparticles, and natural systems such as proteins, cells and their fragments and hybrids. We focus on the intravascular targets including endothelial cells lining the blood vessels, components of blood and the reticuloendothelial system (RES). In order to shift the uptake of circulating DDSs from high-capacity RES sinks, we employ ligands of the epitopes exposed on endothelial cells in vascular areas of interest. These epitopes include cell adhesion molecules (e.g., PECAM, ICAM, VCAM), ACE, PV1 and other endothelial markers. These targeted DDSs offer localization and effects in the lungs, brain and other organs unrivaled by other approaches. Further, DDSs targeting to red blood cells (RBCs) circulate for a prolonged time in the cellular blood fraction and act in the blood in uniquely advantageous fashion. Using DDSs with dual affinity to RBCs and endothelium enables vascular surveillance and transfer to endothelial cells expressing secondary binding sites (RBC hitchhiking). We will discuss DDSs with solo and dual avidity to RBCs and endothelium, enabling unprecedented spatiotemporal control of targeting, nanoscale precision and efficacy of delivery and therapeutic interventions.