Early Cancer Detection with Two-Photon Luminescence From Gold Nanorods

描述（由申请人提供）： 在近红外（NIR）波长的双光子成像是一个强大的工具，允许厚的人体组织样本的拓扑结构和分子信息的调查与标准组织学的分辨率和细节，而不需要外来的荧光团。该技术可以提供具有非常高的灵敏度的非侵入性成像，使其成为用于癌前病变的体内诊断和检测的优秀候选者。使用近红外波长的超短激光脉冲，我们可以激发特定的细胞内和细胞外分子和荧光团，如黄素，弹性蛋白和NADH。这些分子的激发使得能够直接可视化组织形态、细胞代谢和分子途径。本研究项目的目标是使用金纳米棒作为造影剂增强双光子信号和相关的成像深度，用于表征和检测肿瘤病变的体内形态学和化学变化。具体来说，我们将使用金纳米棒的强双光子发光（TPL）特性来增强组织深处肿瘤细胞TPM成像的图像对比度。此外，金纳米棒的大近场散射特性将用于增强来自内在荧光团的双光子自发荧光（TPAF）信号。增强的双光子信号将提供具有与用有机染料的双光子成像中所使用的那些一样低的平均功率的成像。在接下来的几年里，我们设想开发一种新的成像模式，称为“等离子体双光子成像”，可以提供更好的肿瘤描绘。这项研究的目的是补充正在进行的工作，开发一种小型化的内窥镜探头，能够同时成像在体内的生化和形态学变化，更好地描绘癌前病变。这样的工具可以用作非侵入性和成本效益的筛查和诊断技术。

DESCRIPTION (provided by applicant): Two-photon imaging at near-infrared (NIR) wavelengths is a powerful tool that permits the investigation of the topology and molecular information of thick human tissue samples with the resolution and detail of standard histology without the need for extrinsic fluorophores. This technique can provide non-invasive imaging with very high sensitivity making it an excellent candidate for in vivo diagnosis and detection of precancerous lesions. Using ultrashort laser pulses at NIR wavelengths, we can excite specific intracellular and extracellular molecules and fluorophores such as flavins, elastin, and NADH. Excitation of these molecules enables direct visualization of tissue morphology, cell metabolism, and molecular pathways. The goal of this research project is to enhance two photon signal and the associated imaging depth using gold nanorods as contrast agents for the characterization and detection of in vivo morphological and chemical changes in tumor lesions. Specifically, we will use strong two photon luminescence (TPL) properties of gold nanorods to enhance image contrast in TPM imaging of tumor cells deep in the tissue. In addition, the large near-field scattering properties of gold nanorods will be used enhance the signal of two photon autofluorescence (TPAF) from intrinsic fluorophores. The enhanced two-photon signal will provide imaging with average powers as low as those used in two photon imaging with organic dyes. Over the next few years, we envision developing a new imaging modality called "plasmonic two-photon imaging" that can provide better delineation of tumors. This study is designed to complement ongoing work for the development of a miniaturized endoscopic probe capable of simultaneously imaging in vivo both biochemical and morphological changes, for the better delineation of precancerous lesions. Such a tool can be employed as a noninvasive and cost effective screening and diagnostic technique.