A New Strategy for Cancer Detection using Raman Spectroscopy with Nanoparticles

描述（由申请人提供）：该项目的总体目标是使用结合了拉曼光谱和纳米颗粒的内窥镜成像方法来改善癌症的检测。我建议通过一种新的分子成像方法来做到这一点。分子成像将通过使用产生拉曼光散射信号的局部施用的肿瘤靶向的基于金的纳米颗粒和可以用光激发这些纳米颗粒并检测它们的非弹性散射光的拉曼内窥镜来实现。我计划使用多模式方法（microPET和活体显微镜）在活体小鼠模型中研究这些纳米颗粒的自然生物分布。将使用局部应用于口腔、膀胱和子宫颈（所有这些都能够在临床上用内窥镜询问）来研究纳米颗粒给药的各种途径。 并将其分布与静脉注射进行比较。据信，通过局部（即口腔）施用这些金纳米颗粒，由于绕过循环系统，可以避免潜在的不良毒性作用。我还将用显微镜检查纳米颗粒与开放性伤口或脓肿的相互作用，这些伤口或脓肿可能非常接近接受局部纳米颗粒给药的目标区域（即口腔）。一旦它们的生物分布和毒性效应被更彻底地理解，我计划评估这些肿瘤靶向拉曼纳米粒子对新鲜的人类肿瘤组织样本的靶向效率。我打算使用鳞状细胞癌来证明这种一般方法作为第一个目标的原因，肿瘤靶向肽的可用性，降低毒性和需要 以改进检测。由于拉曼内窥镜先前已用于人类，并且由于基于金的纳米颗粒相对惰性，并且一些结构已被FDA批准用于人类，因此该方法预期临床转化的风险较低。从该提案中获得的结果可以显着加速将这种新策略转化为临床。此外，利用拉曼光谱的超灵敏检测和多路复用能力来检测癌症可以作为一种强大的诊断工具，有可能显著影响癌症患者的存活率。

DESCRIPTION (provided by applicant): The overall goal of this project is to improve the detection of cancer using an endoscopic imaging approach that incorporates both Raman spectroscopy and nanoparticles. I propose to do this through a novel molecular imaging approach. The molecular imaging will be accomplished by using topically administered tumor targeted gold based nanoparticles that produce a Raman light scattering signal and a Raman endoscope that can excite these nanoparticles with light and detect their inelastically scattered light. I plan to investigate the natural biodistribution of these nanoparticles using a multimodal approach (microPET and intravital microscopy) in living mouse models. Various routes of nanoparticle administration will be investigated using topical application to the oral cavity, bladder, and cervix (all of which have the ability to be interrogated with an endoscope clinically) and compare their distribution to an intravenous injection. It is believed that by administering these gold nanoparticles topically (i.e. oral cavity) that potential adverse toxicity effects wouldbe avoided due to circumventing the circulatory system. I will also microscopically examine the interaction of nanoparticles with open wounds or abscesses that could potentially be in close proximity to the area of interest (i.e. oral cavity) receiving the topical nanoparticle administraton. Once their biodistribution and toxicity effects are more thoroughly understood I plan to evaluate the targeting efficiency of these tumor targeted Raman nanoparticles on fresh human tumor tissue samples. I intend to use squamous cell carcinoma to demonstrate this general approach as the first target for reasons of tumor targeted peptide availability, reduced toxicity and a need for improved detection. The approach is expected to be low risk for clinical translation because Raman endoscopes have previously been used in humans, and because gold based nanoparticles are relatively inert and some constructs have already been approved by the FDA for human use. The results obtained from this proposal could significantly accelerate the translation of this novel strategy into the clinic. In addition, harnessing the ultrasensitive detection and multiplexing capabilities of Raman spectroscopy for the detection of cancer could serve as a powerful diagnostic tool, with the potential to significantly impact the survival rate o cancer patients.