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

项目摘要/摘要 该项目是我们正在进行的R01项目的C3i Accell行政补充(EB018358“稀土纳米探测器，用于 光学成像和疾病跟踪“)。母公司R01项目正在开发短波红外(SWIR)发光 用于荧光引导手术的纳米颗粒造影剂和成像仪器。在R01项目中， 采用小鼠癌症模型来评估这些造影剂在体内的表现。 通过核心C3I计划，我们了解到这项技术的成功商业化将需要我们 证明造影剂合成的规模可以比我们在R01小鼠研究中使用的体积大得多， 同时保持质量和一致性。我们目前以15毫升的批次合成纳米探针，这些批次 足以完成典型的小鼠纵向实验，但不足以将技术推进到 大型动物模型和人体临床试验。为了使这些未来的研究成为可能，这个C3i Accell项目将开发和 验证在1000毫升规模合成纳米探针的方法。纳米探测器将包含一种掺铒纳米颗粒 提供SWIR光学发射的核心，封装在人血清白蛋白中以实现生物兼容性，与小型 AMD3100分子连接到外表面，用于靶向CXCR4肿瘤生物标记物。在…中保持一致性 纳米探测器的这种规模的特性，并展示一种可扩展的商业生产方法，我们将开发 利用连续流动微流控平台的合成方法。

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.