Recent developments for Nanotherapy for Vulnerable Plaque include:

• Drs. Ruggeri, Mitragotri and Smith collaborated on devising particles that can be delivered to thrombi on vulnerable atherosclerotic lesions. This collaboration is the first project of this PEN to move in vivo. The team was able to combine their work on particle shape with a targeting element comprised of a domain from von Willebrand factor to obtain particles that home to forming thrombi. Fluorescent versions of these particles are able to detect a forming thrombus in a mouse model of vascular injury. This is the first time we are aware that an active thrombus can be imaged in vivo!

• Dr. Zasadinskiís group put forward a highly novel method for enacting the instantaneous release of drugs from nanoparticles. His group has devised approaches for synthesizing multi-compartment vesosomes so that drug is protected from serum lipases within the interior compartment. The team encapsulated hollow gold nanoshells, which can absorb near infrared light and experience highly localized heating, within their vesosomes. They went on to show that irradiation of these new vesosomes with near infrared caused the vesosomes to burst and release their contents. This discovery led to the submission of one patent and one paper.

• Dr. Andrew Clelandís group at UCSB has developed novel electronic sensors capable of reporting on the molecular nature of a sample. It is becoming apparent that these electronic sensing devices have many potentially useful applications in vascular biology and medicine. Dr. Clelandís group has established a collaboration with Dr. Ruggeriís group (TSRI) with the aim of using the electronic sensors to assess the composition of cells and cellular remnants in the blood. This capability could be immensely valuable in characterizing particles in the blood that are derived from cells. Previously the significance of such particles to physiology was not evident, and they were even referred to as cellular ìdust.î However, it is now believed that cell-derived particles play a major role in both inflammation and thrombosis.

• Dr. Mitragotriís group has developed a new nanoparticle that is likely to escape uptake by the reticuloendothelial system, a property that will dramatically increase the half-life of particles in vivo. The groups advance stemmed from their ability to make particles shaped like ìworms,î which they found could not be internalized by macrophages.

• Dr. Ruoslahtiís group has scanned their library of existing peptide targeting elements and found several of these to home to atherosclerotic lesions in mice. This is an exceedingly important advance because it places us in a position to direct almost any particle we choose to plaques.