EAGER: Kinetic and biophysical approach to engineering targeted nanoparticles

University Of California-Irvine, Irvine CA

Investigators

Abstract

1539114(Haun) The purpose of this research project is to develop targeted strategies for the delivery of therapies. The research involves exploration at the interface of binding targets such that the adhesion of targeted therapies is effectually enabled. The research will provide immense benefit through the development and advancement of strategies for treating disease without impairment to healthy cells, tissues and organs. In addition, this research will result in the decrease in the amount of drug therapies required as specificity and targeting is increased. This research will also propel the science of adhesion forward through the understanding of binding properties for surfaces. Improving capabilities to target diseases would change the way the diseases are detected and treated. It would enable early detection and personalized medicine capabilities, as well as lower adverse side-effects. This research project seeks to explore the development of nanomaterials as carriers for targeted delivery platforms. Developed nanomaterials will have high-loading capacities, will enable facile attachment of targeting moieties, and will have favorable pharmacokinetics. The research will involve the development of multo0valent nanoparticles. Adhesion dynamics will be controlled in these nanoparticle delivery systems. The goal for this work is to achieve the first experimental demonstration of superselectivity. The hypothesis is that precisely tuning kinetic and biophysical properties of the molecular binding interactions so that they are highly dynamic will result in exquisite sensitivity to bond valency. In this manner, adhesion to normal cells would only be transient in nature, but firm binding would occur at higher target levels or after de novo expression of a co-target. The hypothesis will be tested using vascular inflammation as a model via the target ICAM-1. The PI postulates that the transient binding paradigm proposed would enable a unique and exciting capability: active surveillance of the vascular wall for sites of disease.