Photoswitchable nanoprobes for in vivo flow cytometry

用于体内流式细胞术的光开关纳米探针

• 批准号: 9279128
• 负责人: Vladimir P Zharov
• 金额: $ 32.53万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-16 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9279128
• 关键词: Activities of Daily Living; Animal Model; Bacteremia; Biological; Biological Assay; Biological Markers; Blood Cells; Blood Circulation; Cancer Biology; Cancer Diagnostics; Cardiovascular system; Cells; Cessation of life; Characteristics; Clinical Trials; Coagulation Process; Color; Communities; Contrast Media; Detection; Development; Devices; Diagnosis; Diagnostic Procedure; Disadvantaged; Disease; Disseminated Malignant Neoplasm; Engineering; Environment; Flow Cytometry; Goals; Health; Health Professional; Human; In Vitro; Individual; Injectable; Injection of therapeutic agent; Intravenous; Label; Lasers; Life Cycle Stages; Malignant Neoplasms; Methods; Molecular; Molecular Target; Monitor; Nanotechnology; Neoplasm Circulating Cells; Neoplasm Metastasis; Pathologic; Physiologic pulse; Physiological; Primary Neoplasm; Procedures; Process; Prognostic Marker; Property; Research; Role; Safety; Sepsis; Site; Techniques; Technology; Testing; Time; Time Study; Toxic effect; Work; cancer cell; cancer recurrence; cancer therapy; cell behavior; clinically relevant; immune system function; improved; in vivo; nanoparticle; nanoprobe; neoplastic cell; personalized medicine; pilot trial; plasmonics; portability; pre-clinical; public health relevance; technology development; tool; trafficking; tumor; tumor progression

DESCRIPTION (provided by applicant): Unprecedented nanotechnological advances hold the promise to revolutionize cancer diagnostics and treatment. Nevertheless despite substantial efforts to understand cancer biology, metastases, which cause up to 90% of cancer deaths, are still poorly understood. Comprehensive studies have demonstrated the tremendous potential of using the number of circulating tumor cells (CTCs) as a marker of metastatic development. Among different CTC assays, in vivo photoacoustic (PA) flow cytometry (PAFC) demonstrates a unique capability for high-throughput, real-time study of CTCs labeled with functionalized nanoparticles (NPs) in the natural biological environment. However, despite the advantages of molecular CTC targeting, conventional labeling procedures make it difficult to track individual CTCs, which are important to understanding the mechanisms of cancer metastasis, including identification of the origin of CTCs (i.e., from primary tumor or from metastases) and the role of re-seeding or self-seeding processes. The goal of this project is to develop a platform for engineering, characterizing and optimizing nonfluorescent spectrally switchable SNPs to be used as PA contrast agents that can track individual CTCs in vivo. We hypothesize that individual CTCs targeted by NPs can be tracked through ultrafast spectral switching of NPs directly in the bloodstream using short laser pulses of specific wavelengths that are followed by real-time PA multicolor monitoring of CTCs containing the switched NPs. We will accomplish our goal test by testing this hypothesis through the following specific aims: (1) develop a platform fo engineering and characterizing spectrally switchable nanoparticles as multicolor photothermal and PA contrast agents; (2) test the capabilities of optimized switchable nanoparticles for bioconjugation and molecular targeting of cancer cells; and (3) study in vivo the properties of switchable nanoparticles and tracking of individual CTCs in the metastatic cascade via an ultrafast photoswitching. Developing this technology will allow in vivo study of CTCs that will clarify the poorly understood mechanisms of early metastatic disease and could help develop advanced diagnosis techniques and individualized therapies. Tracking individually labeled cells can improve our understanding of cell behavior in the circulatory system and provide a unique means of tracking the life cycle of any circulating cell or groups of cells. This ability can enabl the research community to discover and assess the physiological and pathological mechanisms related to health and diseases, including studies of immune system function, bacteremia, sepsis and clotting at the single cell level. The proposed technology is an advanced research tool for use in pre-clinical animal models and has the potential to be approved for human use because PA flow cytometry is safely used in humans and several NPs have been approved for pilot trials.

描述（由申请人提供）：前所未有的纳米技术进步有望改变癌症诊断和治疗。然而，尽管努力理解癌症生物学，但导致多达90％的癌症死亡的转移试剂仍然很少了解。全面的研究表明，使用循环肿瘤细胞（CTC）作为转移性发育的标志的巨大潜力。在不同的CTC分析中，体内光声（PA）流式细胞仪（PAFC）证明了自然生物学环境中用功能化纳米颗粒（NPS）标记的CTC的高通量，实时研究的独特能力。然而，尽管分子CTC靶向具有优势，但常规的标记程序使得很难跟踪单个CTC，这对于理解癌症转移的机制至关重要，包括鉴定CTC的起源（即来自原发性肿瘤或转移的起源）以及重生或自我播种或自我播种过程的作用。该项目的目的是开发一个工程平台，表征和优化非荧光频谱可切换的SNP，以用作可以在体内跟踪单个CTC的PA对比剂。我们假设可以使用特定波长的短激光脉冲直接在血液中通过NPS的超快光谱切换来跟踪NPS靶向的单个CTC，这些脉冲随后是含有开关NP的CTC的实时PA多色监测。我们将通过以下特定目的测试该假设来完成我们的目标测试：（1）开发一个平台FO工程，并将频谱可切换的纳米颗粒作为多色光热和PA对比剂; （2）测试优化可切换纳米颗粒的功能，用于癌细胞的生物缀合和分子靶向； （3）在体内研究可切换纳米颗粒的特性，并通过超快速拍照进行转移级联中的单个CTC跟踪。开发这项技术将允许对CTC进行体内研究，这些研究将阐明早期转移性疾病的机制知之甚少，并可以帮助开发先进的诊断技术和个性化疗法。跟踪单独标记的细胞可以提高我们对循环系统细胞行为的理解，并提供一种独特的方法来跟踪任何循环细胞或细胞组的生命周期。这种能力可以使研究界能够发现和评估与健康和疾病有关的生理和病理机制，包括对单个细胞水平的免疫系统功能，菌血症，败血症和凝结的研究。提出的技术是用于临床前动物模型中的高级研究工具，并且有可能被批准用于人类使用，因为PA流式细胞仪安全地用于人类，并且已批准了一些NP进行试验试验。