Investigating Tumor Growth Dynamics Using Multimodal Contrast Agents and Optical

使用多模式造影剂和光学研究肿瘤生长动力学

• 批准号: 7830248
• 负责人: Alexander Wei
• 金额: $ 50万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7830248
• 关键词: Address; Area; Biomechanics; Carcinoma; Cells; Coculture Techniques; Complement; Contrast Media; Development; Extravasation; Fibroblasts; Histology; Image; In Vitro; Magnetism; Measurement; Measures; Mechanics; Metric; Multimodal Imaging; Mus; Optical Coherence Tomography; Optics; Plastics; Property; Resolution; Technology; Tensile Strength; Three-Dimensional Imaging; Tissues; Tumor Tissue; Visual; macrophage; migration; nanoparticle; nanoprobe; neoplastic cell; optical imaging; physical science; tumor; tumor growth; tumor xenograft; Address; Area; Biomechanics; Carcinoma; Cells; Coculture Techniques; Complement; Contrast Media; Development; Extravasation; Fibroblasts; Histology; Image; In Vitro; Magnetism; Measurement; Measures; Mechanics; Metric; Multimodal Imaging; Mus; Optical Coherence Tomography; Optics; Plastics; Property; Resolution; Technology; Tensile Strength; Three-Dimensional Imaging; Tissues; Tumor Tissue; Visual; macrophage; migration; nanoparticle; nanoprobe; neoplastic cell; optical imaging; physical science; tumor; tumor growth; tumor xenograft

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-CA-116: Physical Sciences and Cellular Mechanics. We will develop analytical imaging capabilities with complementary nanoparticle probes to measure the viscoelastic properties of cells and tissues in a noninvasive manner. These capabilities will be applied toward understanding biomechanical factors on tumor growth dynamics. Near-infrared (NIR) absorbing Au nanoparticles with magnetic cores will serve as multimodal contrast agents for multiphoton imaging and for magnetomotive optical coherence tomography (MM-OCT) and elastography (MM-OCE), to characterize viscoelastic changes in tumor cells and tissues as a function of their development. Tumor cells will be laden with nanoprobes and cocultured with fibroblasts or macrophages for in vitro multimodal imaging with MM-OCE. Tumor xenografts will also be grown in mice from nanoprobe-laden tumor cells, then excised for ex vivo imaging with results collated with conventional metrics of tumor development (i.e., visual inspection and histology). We anticipate this approach can reveal critical biomechanical differences in the development of invasive carcinomas, in which cells undergo transformations from turgid states with high tensile strength to plastic and deformable states associated with migration and extravasation. Our Specific Aims are as follows: 1) Construction of an integrated optical platform for optical coherence tomography (OCT) and elastography (OCE), for noninvasive imaging of tumor tissues with cellular resolution; 2) Fabrication of nanoprobes that combine plasmon resonance with magnetomotive activity, to generate unique NIR signatures for 3D imaging and elastography; 3) Optimization and deployment of the multimodal imaging platform for simultaneous structural imaging and viscoelastic profiling of nanoprobe-laden tumor cells and excised tumor tissues.

描述（由申请人提供）：此申请介绍了广泛的挑战领域（06）启用技术和特定挑战主题，06-CA-116：物理科学和蜂窝力学。我们将使用互补的纳米粒子探针开发分析成像能力，以无创的方式测量细胞和组织的粘弹性。这些能力将用于理解肿瘤生长动力学的生物力学因素。带有磁芯吸收的Au纳米颗粒的近红外（NIR）将用作多模式对比剂的多模式对比剂，用于多型对比剂，用于磁性光学相干断层扫描（MM-OCT）和弹性摄影（MM-OCE），以表征肿瘤细胞和组织中的粘弹性变化，以表征其发育的功能。肿瘤细胞将用纳米探针载体，并与成纤维细胞或巨噬细胞共培养，用于用MM-OCE进行体外多模式成像。肿瘤异种移植物还将在纳米探针肿瘤细胞的小鼠中生长，然后切除以进行体内成像，结果与肿瘤发育的常规指标（即视觉检查和组织学）相结合。我们预计这种方法可以揭示在侵入性癌的发展中的关键生物力学差异，在这种癌中，细胞从具有高抗拉力强度的turgid状态转变为塑性和可变形状态，与迁移和渗出相关。我们的具体目的如下： 1）构建用于光学相干断层扫描（OCT）和的集成光学平台和 弹性图（OCE），用于对具有细胞分辨率的肿瘤组织的无创成像； 2）将等离子体共振与磁光活性相结合的纳米探针制造 为3D成像和弹性产生独特的NIR签名； 3）用于同时结构的多模式成像平台的优化和部署 纳米探针肿瘤细胞和切除的肿瘤组织的成像和粘弹性分析。