Rare earth nanoprobes for optical imaging and disease tracking (C3i)

项目概要/摘要 该项目是C3 i Accell对我们正在进行的R 01项目（EB 018358“用于 光学成像和疾病跟踪”）。R 01的母项目是开发短波红外（SWIR）发光 纳米粒子造影剂和用于荧光引导手术的成像仪器。在R 01项目中， 采用癌症的小鼠模型来评价这些造影剂的体内性能。 通过核心C3 i计划，我们了解到这项技术的成功商业化将要求我们 证明造影剂合成可以按比例放大到比我们的R 01鼠研究中使用的体积大得多的体积， 同时保持质量和一致性。我们目前合成的纳米探针在个别15毫升批次， 足以完成一个典型的纵向鼠实验，但不足以推动技术向前发展， 大型动物模型和人体临床试验。为了使这些未来的研究，这个C3 i Accell项目将开发和 验证以1000 ml规模合成纳米探针的方法。纳米探针将包含掺铒纳米颗粒 核心提供SWIR光发射，封装在人血清白蛋白中以实现生物相容性， 分子AMD 3100缀合至外表面以靶向CXCR 4肿瘤生物标志物。保持…的一致性 纳米探针在这个规模的性质，并证明商业生产的可扩展的方法，我们将开发 使用连续流动微流体平台的合成方法。

PROJECT SUMMARY / ABSTRACT This project is a C3i Accell administrative supplement to our ongoing R01 project (EB018358 “Rare-earth nanoprobes for optical imaging and disease tracking”). The parent R01 project is developing short-wave infrared (SWIR) light-emitting nanoparticle contrast agents and imaging instrumentation for use in fluorescence-guided surgery. In the R01 project, mouse models of cancer are employed to evaluate the performance of these contrast agents in vivo. Through the core C3i program, we learned that successful commercialization of this technology will require us to demonstrate that contrast agent synthesis can be scaled to much larger volumes than used in our R01 murine studies, while maintaining quality and consistency. We currently synthesize nanoprobes in individual 15 ml batches which are sufficient to complete a typical longitudinal murine experiment, but inadequate for moving the technology forward into large animal models and in-human clinical trials. To enable these future studies, this C3i Accell project will develop and validate methods to synthesize nanoprobes at the 1000 ml scale. Nanoprobes will contain an erbium-doped nanoparticle core providing SWIR optical emissions, encapsulated in human serum albumin for biocompatibility, with the small molecule AMD3100 conjugated to the outer surface for targeting the CXCR4 tumor biomarker. To maintain uniformity in nanoprobe properties at this scale and to demonstrate a scalable approach for commercial production, we will develop synthesis methods using a continuous flow microfluidic platform.