The goal of this CAREER plan is to create and utilize a novel sensing system called the "holey scaffold" to nondestructively and minimally invasively measure dynamic nanoparticle transport and photothermal and photochemical tumor response to nanoparticle-mediated laser therapy. A holey scaffold is a new technology co-invented by the PI that is composed of an embedded network of microchannels within a scaffold framework upon which cells and tissues can be grown. Hollow core fibers integrated in the holey scaffold permit simultaneous optical sensing/imaging of dynamic processes and selective delivery of biological agents (e.g. nutrients, cells, nanoparticles) for control of biochemical responses. The CAREER objective is to use holey scaffolds to measure 1) spatiotemporal nanoparticle transport for varying nanoparticle properties, targeting approaches, and delivery methods, 2) dynamic photothermal response (temperature, heat shock protein expression, and cell injury), and 3) real-time photochemical response (reactive oxygen species production) associated with nanoparticle-mediated laser therapies. The versatility of holey scaffolds will enable the first measurement of dynamic tumor response in vitro within a bioreactor system and in vivo in a mouse tumor model. Measured tumor response will be utilized to create a novel computational model for predicting tumor response and optimizing implementation of nanoparticles in laser therapy.
