Acoustic Imaging of Sentinel Node Matastasis using Plasmonic Nanosensors

描述（由申请人提供）：在癌症患者中，确定恶性肿瘤是否扩散是制定治疗计划和预测预后的最重要因素。在大多数情况下，癌细胞最初通过局部淋巴结扩散。因此，临床评估区域淋巴结转移的存在是至关重要的。不幸的是，目前还没有实时、无创的临床方法可以可靠地检测和诊断淋巴结的微转移。因此，临床迫切需要一种广泛可用、无创、操作简单、安全、能够实时可靠地检测和充分诊断淋巴结微转移的成像技术。我们研究项目的总体目标是开发一种先进的，体内的，无创的，分子特异性成像技术，即集成超声和光声成像结合靶向等离子体纳米传感器，能够即时准确地实时评估前哨淋巴结微转移。本项目的基本假设是光声成像与广泛应用的临床超声成像相结合是可能的，超声和光声成像可以实时进行，从而产生即时诊断并允许早期实施治疗。为了充分探索分子特异性超声和光声淋巴（MS-USPAL）成像在前哨淋巴结微转移的检测和表征方面的能力，必须解决广泛的科学和工程、生物医学和临床问题。目前的应用主要集中在MS-USPAL成像的临床翻译的重要方面。我们将为MS-USPAL开发和验证临床可翻译的等离子体纳米传感器。我们将使用超小的金纳米颗粒靶向表皮生长因子受体（EGFR），表皮生长因子受体在鳞状癌和许多其他上皮肿瘤中过表达。为了对癌细胞进行高灵敏度检测，我们将探索EGF受体介导的内吞作用以及紧密间隔的分子特异性纳米颗粒之间的等离子体共振耦合的影响。纳米颗粒的超小尺寸将非常有利于从体内快速清除，从而允许安全过渡到临床实践。此外，5nm配体覆盖的金纳米颗粒将大大减少非特异性相互作用，减少免疫细胞（如淋巴结炎症引起的巨噬细胞）对纳米颗粒的摄取，从而减少假阳性结果。此外，我们将设计和构建一个临床MS-USPAL成像系统的原型，该系统能够在体内对5纳米纳米颗粒进行成像。

DESCRIPTION (provided by applicant): In cancer patients, determination of whether a malignancy has spread is the single most important factor used to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is of paramount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliably detect and diagnose micrometastases in lymph nodes. Therefore, there is an urgent clinical need for an imaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliably detect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in-vivo, noninvasive, molecular specific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targeted plasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph node micrometastases in real time. The underlying hypothesis of this project is that photoacoustic imaging integrated with widely used clinical ultrasound imaging is possible and both ultrasound and photoacoustic imaging can be performed in real time, yielding an immediate diagnosis and allowing early implementation of treatment. A wide range of scientific and engineering, biomedical and clinical problems must be addressed to fully explore the capabilities of molecular specific ultrasound and photoacoustic lymphatic (MS-USPAL) imaging in detection and characterization of sentinel lymph node micrometastases. The current application is focused on important aspects of clinical translation of MS-USPAL imaging. We will develop and validate clinically translatable plasmonic nanosensors for MS-USPAL. We will use ultra-small gold nanoparticles to target epidermal growth factor receptor (EGFR), which is overexpressed in squamous carcinoma and in many other epithelial neoplasms. For highly sensitive detection of cancer cells, we will explore EGF receptor mediated endocytosis and the effect of plasmon resonance coupling between closely spaced molecular specific nanoparticles. The ultra-small size of nanoparticles will be highly favorable for rapid clearance from the body which will allow safe transition into clinical practice Additionally, 5 nm ligand capped gold nanoparticles will greatly reduce nonspecific interactions and reduce the uptake of nanoparticles by immune cells such as macrophages present due to lymph node inflammation, thus diminishing false positive results. Furthermore, we will design and construct a prototype of the clinical MS-USPAL imaging system capable of imaging 5 nm nanoparticles in-vivo.