This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). This Small Business Technology Transfer (STTR) Phase I project will develop a new class of multifunctional nanoparticle assemblies for optical disease diagnosis and treatment. The nanoparticle assemblies will be synthesized using a new plasmon-enhanced two-photon activated crosslinking approach that will attach nanoparticles with an unprecedented level of selectivity towards specific nanoparticle sites. Through incorporation of organic chromophores, the plasmonic resonances of the metallic nanoparticles will provide three to six orders of magnitude enhancement in the efficiency of second harmonic imaging microscopy and two-photon excitation fluorescence microscopy, which will be utilized for imaging the locations of disease states such as cancerous tumors within the body. Increased laser intensity combined with the energy concentration of the plasmonic hotspots into small spatial volumes will enable hyperthermal treatment of the disease through large increases in the local temperature. The broader impacts of this research include acceleration of the development of optical techniques for diagnosis and treatment of diseases such as cancer. While such optical techniques are under intense research and development for implementation in biomedicine, the orders of magnitude increases in efficiency provided by the new nanoparticle assemblies proposed here will enable more rapid implementation. Furthermore, the novel approach for synthesis of nanoparticle assemblies will have a much broader scientific and commercial impact. The assembly method only requires that one of the nanoparticles be metallic. The development of this new assembly approach will thus enable the combination of a wide range functionalities including magnetic nanoparticles, antimicrobial silver nanoparticles, and fluorescent quantum dots
