RARE EARTH NANOPROBES FOR OPTICAL IMAGING AND DISEASE TRACKING

项目概要： R 01更新提案旨在推进下一代光学纳米材料 用于体内病变的超灵敏检测的探针，其应用于荧光- 引导手术（FGS）。FGS这一新兴领域目前缺乏光学对比度的流水线 可以照亮这种深层病变的试剂，以允许实时检测和精确测量。 由肿瘤外科医生切除。 我们之前的R 01项目开发了第一代病变靶向光学探针 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， 对于FGS应用不是最佳的。它们具有相对高的信号衰减， 用于激发的近红外（NIR）光，其较短的穿透深度限制了 到达并检测到更深处的病变。因此，本次R 01续期申请将重点关注 继续我们的进步，设计显着更明亮的回旋发射纳米探针，而 沿着沿着两条重要的途径拓宽了短波红外成像的背景：首先，我们希望 开发一类数量级更亮的SWIR发射纳米复合材料， 使用SWIR光激发，假设它们可以使用更深的穿透力激发 红外线，这将开辟照明周围的癌症更深的应用程序 腹膜后淋巴结（Aim 1A），并将其精确定位于手术床上的癌症病灶 (Aim 1B）。其次，我们的目标是开发一个活体短波红外成像平台，可以引导 精确检测体内小的癌症簇（Aim 2A），并对手术部位进行分子定位。 一个用于划分肿瘤病灶、淋巴结和主动脉旁血管解剖标志的床 内皮细胞（Aim 2A）。我们将扩展这个活体成像平台， 切除，并证明相对于现有的指导下的切除结果上级 荧光团和我们的第一代NIR可激发RE纳米探针（Aim 2B）。的成果 目的2将证明使用卵巢癌腹膜转移和减积模型。 该项目的总体影响将是基于纳米技术的监控设计 一种新的造影剂，可以集成在短波红外线， 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.