? The central aim of this proposal is to understand ultrafast light-DNC interactions as monitored by high frequency ultrasound. In particular, we will use ultrasonic micrsocopy to monitor the photodisruption process transducing site-targeted nanoparticles into a detectable microbubble. Our short-term goal is to detect molecular agents targeted to squamous cell cancers and to monitor therapy applied to these cells. We propose to investigate two photodisruption regimes: one near threshold in which the UOB process can be carefully controlled to produce detectable microbubbtes with little cellular injury (i.e., minimally invasive); the second at a different set of optical parameters where the UOB processes can be highly destructive, killing labeled cells for therapeutic purposes, ff both regimes can be established, then ultrasonic detection of DNC promoted photodisruption can provide a sensitive tool for both site-targeted molecular imaging and molecular therapeutics. ? ? It is the aim, therefore, of the work proposed here to address the following issues in detail. ? ? 1.) Characterize LIOB and resultant microbubbles in water, water-based gels, and tissue culture using high-frequency ultrasound. In particular, the ultrasound system will monitor photodisruption thresholds, system parameters for minimally invasive transient bubble creation, system parameters for invasive and stable bubble creation, system parameters determining bubble size, and system parameters determining bubble temperature. ? 2.) Determine the necessary composition and structure of DNC particles that have minimal LIOB thresholds. Detailed structural studies will be performed on all compositions showing enhanced breakdown characteristics. ? 3.) Determine the range of optical parameters controlling LIOB thresholds and photodisruption characteristics in DNC solutions and DNC loaded tissue-equivalent gelatin phantoms, including wavelength, optical fluence per pulse, repetition rate, and total number of pulses. ? ? If these studies demonstrate that we can control DNC-promoted LIOB to operate either as a minimally invasive sensor or a highly localized disruptor, and we can sensitively monitor both processes with high frequency ultrasound, we will develop an RO1 proposal for site-targeted molecular imaging and therapy monitoring of squamous cell cancers, a rapidly growing and very important clinical problem. ? ?
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