Nanosensor probes for oxygen imaging in vivo

用于体内氧成像的纳米传感器探针

• 批准号: 7094604
• 负责人: DAVID F WILSON
• 金额: $ 36.4万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094604
• 关键词: bioimaging /biomedical imaging; biotechnology; clearance rate; fluorescence microscopy; fluorescent dye /probe; free radical scavengers; hypoxia; laboratory mouse; metalloporphyrins; microcirculation; molecular probes; nanotechnology; neurochemistry; newborn animals; oxygen transport; pharmacokinetics; phosphorescence; polyethylene glycols; swine; technology /technique development; three dimensional imaging /topography; toxicology

DESCRIPTION (provided by applicant): Oxygen dependent quenching of phosphorescence is a sensitive and robust method for measuring molecular oxygen, particularly in tissue in vivo. It has been demonstrated that 3D imaging of oxygen in tissue can be accomplished using near infrared light when near-infrared absorbing phosphorescent oxygen sensors are added to the blood. We propose to develop non-toxic optical nanosensors suitable for measuring and imaging oxygen in tissue microvascualture in vivo, ready for translation into clinics. We will synthesize bio-compatible oxygen nanosensors with near infrared absorption and emission and quenching constants optimized for measurements in tissue. The phosphors will be multi-layered, i.e. metal complexes of tetrabenzoporphyrins, encapsulated inside dendrimers and coated with oligoethyleneglycols (PEG). The near-infrared absorbing luminescent metalloporphyrins will act as the actual sensors for oxygen. Dendrimers will be covalently linked to the porphyrins to form protective shells, tuning oxygen diffusion rates to the values optimal for tissue oxygen measurement. The dendritic shells will also help to protect the porphyrin core from interacting with blood components and will serve as scavengers for singlet oxygen. Porphyrin dendrimers will then be targeted for rapid excretion (via the kidney) by coating their external surfaces with PEGs. PEGs will isolate the porphyrin-dendrimers from interactions with other blood components. Thus, the sensor luminescence intensity and lifetime will become completely insensitive to species in the environment other than oxygen. Acute and long term toxicity of the nanosensors will be exhaustively tested in the newborn piglet model and mice model, respectively. The goal is to create a nanosensor(s) for oxygen that is suitable for clinical use, moving it to the point where it is ready for translation into the clinics i.e. ready for larger scale synthesis and rigorous toxicology studies preparatory to use in clinical trials.

描述(申请人提供)：氧依赖的磷光猝灭是一种灵敏和可靠的测量分子氧的方法，特别是在活体组织中。已经证明，当在血液中添加近红外吸收磷光氧传感器时，可以使用近红外光完成组织中氧的3D成像。我们建议开发无毒的光学纳米传感器，适用于体内组织微血管培养中的氧气测量和成像，并准备转化为临床。我们将合成生物相容的氧纳米传感器，具有近红外吸收和发射，以及最适合组织测量的猝灭常数。荧光粉将是多层的，即四苯并卟啉的金属络合物，包裹在树枝状大分子中，并包裹有低聚乙二醇类(PEG)。近红外吸收发光的金属卟啉将作为氧气的实际传感器。树枝状大分子将与卟啉共价连接，形成保护壳，将氧气扩散速度调节到组织氧气测量的最佳值。树枝状外壳还将有助于保护卟啉核心不与血液成分相互作用，并将作为单线态氧的清除剂。然后，通过在它们的外表面涂上钉子，目标是快速排泄(通过肾脏)的卟啉树枝状大分子。PEGS将从与其他血液成分的相互作用中分离出卟啉-树状大分子。因此，传感器的发光强度和寿命将变得对环境中除氧以外的物种完全不敏感。纳米传感器的急性毒性和长期毒性将分别在新生仔猪模型和小鼠模型中进行详尽的测试。其目标是创造一种适合临床使用的氧气纳米传感器(S)，将其移动到准备转化为临床的点，即准备好进行更大规模的合成和严谨的毒理学研究，准备用于临床试验。