A New Strategy for Cancer Detection using Raman Spectroscopy with Nanoparticles

使用纳米颗粒拉曼光谱检测癌症的新策略

• 批准号: 8700750
• 负责人: Cristina L. Zavaleta
• 金额: $ 19.39万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700750
• 关键词: Abscess; Area; Binding; Biodistribution; Bladder; Blood; Cancer Detection; Cancer Patient; Cardiovascular system; Cell Line; Cervix Uteri; Clinic; Clinical; Clinical Research; Contrast Media; Control Groups; Data; Detection; Devices; Diagnostic; Disease; Endoscopes; Endoscopy; Evaluation; Exposure to; FDA approved; Fingerprint; Goals; Gold; Health; Human; Image; Imaging Device; Integrins; Label; Life; Light; Malignant Epithelial Cell; Malignant Neoplasms; Microscope; Optics; Oral cavity; Peptides; Process; Property; Radioactive; Radiolabeled; Radionuclide Imaging; Raman Spectrum Analysis; Reporter; Research; Route; Signal Transduction; Squamous cell carcinoma; Stream; Surface; Surface Properties; Survival Rate; Techniques; Time; Tissue Sample; Tissues; Topical application; Toxic effect; Translating; Translations; Tumor Tissue; Work; base; cancer site; clinical risk; experience; human tissue; improved; in vivo; interest; intravenous administration; intravenous injection; intravital microscopy; light scattering; molecular imaging; mouse model; nanoparticle; nanosized; novel; novel strategies; open wound; overexpression; protein aminoacid sequence; radiotracer; ratiometric; tool; tumor; wound

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.

描述（由申请人提供）：该项目的总体目标是使用结合拉曼光谱和纳米颗粒的内窥镜成像方法来改进癌症的检测。我建议通过一种新颖的分子成像方法来做到这一点。分子成像将通过使用局部施用的肿瘤靶向金基纳米粒子来完成，该纳米粒子产生拉曼光散射信号，以及拉曼内窥镜可以用光激发这些纳米粒子并检测它们的非弹性散射光。我计划在活体小鼠模型中使用多模式方法（microPET 和活体显微镜）研究这些纳米颗粒的自然生物分布。将通过局部应用于口腔、膀胱和子宫颈（所有这些都能够在临床上用内窥镜进行检查）来​​研究纳米颗粒给药的各种途径 并将它们的分布与静脉注射进行比较。人们相信，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。我还将在显微镜下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感兴趣区域（即口腔）。一旦更彻底地了解它们的生物分布和毒性作用，我计划评估这些肿瘤靶向拉曼纳米颗粒对新鲜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通用方法作为第一个目标，因为肿瘤靶向肽的可用性、毒性降低和需求 以改进检测。该方法预计临床转化风险较低，因为拉曼内窥镜之前已用于人类，并且金基纳米颗粒相对惰性，并且一些结构已获得 FDA 批准用于人类。从该提案中获得的结果可以显着加速这一新策略向临床的转化。此外，利用拉曼光谱的超灵敏检测和多重功能来检测癌症可以作为一种强大的诊断工具，有可能显着影响癌症患者的生存率。