CAREER: "Holey Scaffold" Sensing System for Characterization of the Spatiotemporal Tumor Response to Nanoparticle-Mediated Photothermal and Photochemical Therapy

这项职业计划的目标是创造和利用一种被称为“孔支架”的新型传感系统，以非破坏性和最小的侵入性测量纳米颗粒的动态传输以及光热和光化学肿瘤对纳米颗粒介导的激光治疗的反应。多孔支架是由PI共同发明的一项新技术，它由支架框架内嵌入的微通道网络组成，细胞和组织可以在其上生长。集成在多孔支架中的中空核心纤维允许同时对动态过程进行光学传感/成像，并选择性地输送生物制剂(例如营养物质、细胞、纳米颗粒)以控制生化反应。其职业目标是使用多孔支架测量1)不同纳米颗粒性质、靶向途径和输送方法的时空传输，2)动态光热响应(温度、热休克蛋白表达和细胞损伤)，以及3)与纳米颗粒介导的激光治疗相关的实时光化学反应(活性氧产生)。多孔性支架的多功能性将使首次在生物反应器系统内和在小鼠肿瘤模型中测量体外动态肿瘤反应成为可能。测量的肿瘤反应将被用来创建一种新的计算模型，用于预测肿瘤反应和优化纳米颗粒在激光治疗中的实施。

0955072RylanderThe 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.