Nanotherapy for Vulnerable Plaque


Project Number

HL80718

Active Period

Current PEN          2005-2010

Web Site

Budget

$10.5 Million ca.

Consortuim

The Burnham Institute
University of California - Santa Barbara
The Scripps Research Institute

Principal Investigators

Jeffrey Smith
The Burnham Institute
10901 North Torrey Pines Road
La Jolla, CA 92037
phone: +1 585 646-3121
fax: +1 858 646-3192
jsmith@burnham.org


Aims

The long-term objective of this Program of Excellence in Nanotechnology (PEN) is to design nanodevices for the analysis, diagnosis, monitoring, and treatment of vulnerable atherosclerotic plaques. It is generally believed that the rupture of atherosclerotic plaques accounts for ~70% of myocardial infarcts. Plaques differ in their structure and composition. Those with a thin fibrous cap, increased lipid content, and adherent inflammatory cells are referred to as "vulnerable" and are highly susceptible to rupture. This PEN is a partnership between The Burnham Institute (La Jolla, Ca), The Scripps Research Institute (La Jolla, Ca), and the California NanoSystems Institute (CNSI) at the University of California at Santa Barbara. We will use the underlying biochemistry that drives the pathophysiology of atheroma as a wedge to target and control nanodevices directed to vulnerable plaque. This PEN will work at the interface of biochemical design and nanoscience. We will create five fundamental and modular building blocks; Targeting Elements, Delivery Vehicles, Selfassembling Polymers, Molecular Switches, and Bio-Nanoelectromechanical systems (Bio-NEMS). These building blocks will serve as a platform for the creation of novel nanodevices for treating atheroma.

There are six specific aims for this project:

Specific Aim #1: Select for Targeting Elements (TEs) that can be used to deliver nanodevices to the endothelium in and around vulnerable plaque. The TE will be based upon homing peptides selected by in vivo phage display with animal models of atheroma.

Specific Aim #2: Build Delivery Vehicles (DVs) that can be used to transport drugs, imaging agents, nanosensors, and other nanodevices to sites of vulnerable plaque.

Specific Aim #3: Design a series of Self-assembling Polymers (SAPs) that can be used as molecular nanostents to physically stabilize vulnerable plaque, and ultimately to replace the fibrous cap with an anti-adhesive, anti-inflammatory surface.

Specific Aim #4: Devise protein-driven Molecular Switches (MS) that can sense and respond to the pathophysiology of atheroma. The MS will take advantage of the in-depth knowledge on the composition of atheroma and on its local environment.

Specific Aim #5: Devise Bio-nanoelectromechanical systems (Bio-NEMS) capable of sensing and responding to vulnerable plaque.


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