RARE EARTH NANOPROBES FOR OPTICAL IMAGING AND DISEASE TRACKING

项目概要： R01更新提案旨在推进下一代光学纳米材料 用于超灵敏检测体内病变病变的探针，并应用于荧光- 引导手术（FGS）。 FGS新兴领域目前缺乏光学对比度的管道 可以照亮此类深层病变的药剂，以实现实时检测和精确定位 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 对于 FGS 应用来说不是最佳的。它们的信号衰减相对较高，需要 用于激发的近红外 (NIR) 光，其较短的穿透深度限制了 到达并检测更深层次的病变。因此，本次R01续签申请将重点关注 通过设计更亮的短波红外发射纳米探针来继续我们的进步，同时 沿着两个重要途径拓宽短波红外成像的背景：首先，我们渴望 开发一类亮度更高的短波红外发射纳米复合材料 使用短波红外光激发，假设它们可以使用更深穿透的激发 红外光，这将开辟照亮更深层次癌症的应用 腹膜后淋巴结（目标 1A），并在手术床上将其精确定位到癌症病灶 （目标 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 体内精确检测小癌症簇（目标 2A）并对手术进行分子图谱绘制 用于标定肿瘤病变、淋巴结和主动脉旁血管的解剖标志的床 内皮细胞（目标 2A）。我们将扩展这个活体成像平台来指导完整的 切除并表现出相对于现有指导的更好的切除结果 荧光团和我们的第一代 NIR 可激发 RE 纳米探针 (Aim 2B)。结果 目标 2 将使用卵巢癌腹膜转移和减灭模型进行演示。 该项目的总体影响将是基于纳米监控技术的设计 一种可以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.