RARE EARTH NANOPROBES FOR OPTICAL IMAGING AND DISEASE TRACKING

项目总结： 这份R01更新提案旨在推进下一代光学纳米材料 用于体内病变病变的超灵敏检测的探针及其在荧光分析中的应用 引导手术(FGS)。FGS的新兴领域目前缺乏光学对比度的管道 能够照亮这种深层次损伤的代理，以实现实时检测和精确 由肿瘤外科医生切除。 我们之前的R01项目开发了第一代病变靶向光学探头 基于稀土(RE)掺杂的纳米复合材料，可以在体内描绘癌症病变，但 并不是FGS应用的最佳选择。它们具有相对较高的信号衰减，并且需要 用于激发的近红外(NIR)光，其较短的穿透深度限制了 触及并检测更深层次的损伤。因此，本次R01续费申请将重点关注 继续我们的进步，设计出更明亮的SWIR发射纳米探测器，同时 沿着两条重要途径拓宽SWIR成像的背景：第一，我们渴望 开发一类亮度更高的SWIR纳米复合材料，这种复合材料可以 用SWIR光激发，假设他们可以用更深的穿透力激发 红外光，这将在照明更深层次的癌症方面开辟应用 腹膜后结节(目标1A)，并精确定位于手术床上的癌症病变 (目标1B)。其次，我们的目标是开发一个可以指导的活体SWIR成像平台 体内小癌团的精确检测(目标2A)和外科手术的分子图谱 BED用于划定肿瘤病变、淋巴结和主动脉旁血管的解剖标志 血管内皮细胞(Aim 2A)。我们将扩展这个活体成像平台，以指导完成 切除并显示出比现有的指导下更好的切除结果 荧光团和我们的第一代近红外可激发稀土纳米探针(目标2B)。其结果是 目的2将使用卵巢癌腹膜转移和去瘤模型进行验证。 该项目的总体影响将是基于监视纳米技术的设计 一种可集成在短波红外光中的新型造影剂 用于荧光手术指导的成像平台技术。

PROJECT SUMMARY: This R01 renewal proposal aims to advance the next generation of optical nanomaterial probes for ultrasensitive detection of diseased lesions in vivo, with applications to fluorescence- guided surgery (FGS). The emerging field of FGS currently lacks the pipeline of optical contrast agents that can illuminate such deep-seated lesions to permit real-time detection and precise excision by oncosurgeons. Our previous R01 project developed the first generation of lesion-targeted optical probes based on rare-earth (RE)-doped nanocomposites that can delineate cancer lesions in vivo but are not optimal for FGS applications. They have relatively high signal attenuation and require near-infrared (NIR) light for excitation, whose shorter penetration depth limits the ability to reach and detect deeper-seated lesions. Therefore, this R01 renewal application will focus on continuing our advance by designing significantly brighter SWIR-emitting nanoprobes, while broadening the context for SWIR imaging along two important pathways: First, we aspire to develop a class of an order-of-magnitude brighter SWIR emitting nanocomposites that can be excited using SWIR light, with the hypothesis that they can be excited using deeper-penetrating IR light, which will open up applications in illuminating cancers around deeper-seated retroperitoneal nodes (Aim 1A) and precisely target these to cancer-lesions in the surgical bed (Aim 1B). Secondly, we aim to develop a live-subject SWIR imaging platform that can guide precision detection of small cancer clusters in vivo (Aim 2A) and molecularly map the surgical bed to demarcate anatomical landmarks of tumor lesions, lymph nodes and para-aortic vessel endothelium (Aim 2A). We will extend this live-subject imaging platform to guide complete excision and demonstrate superior excision outcomes relative to those guided by existing fluorophores and our first generation NIR excitable RE nanoprobes (Aim 2B). The outcomes of Aim 2 will be demonstrated using an ovarian cancer peritoneal metastasis and debulking model. The overall impact of this project will be on the design of a surveillance nanotechnology based on a new class of contrast agents that can be integrated within a short wave infrared-light imaging platform technology for fluorescence-surgery guidance.