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: 7585703
• 负责人: DAVID F WILSON
• 金额: $ 30.59万
• 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 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7585703
• 关键词: Acute; Acute Toxicity Tests; Affect; Albumins; Animal Model; Area; Binding; Biological; Blood; Blood Vessels; Blood specimen; Bovine Serum Albumin; Brain Hypoxia-Ischemia; Calibration; Clinic; Clinical; Clinical Trials; Collaborations; Complex; Dendrimers; Dependency; Development; Diffuse; Diffusion; Disease; Encapsulated; Environment; Evaluation; Excretory function; Family; Freezing; Future; Generations; Goals; Growth; Hypoxia; Image; Imaging technology; In Vitro; Ions; Kidney; Kinetics; Length; Light; Link; Malignant Neoplasms; Maps; Measurement; Measures; Metalloporphyrins; Methods; Microscopy; Modality; Modeling; Modification; Molecular; Mus; Newborn Infant; Optical Methods; Optics; Outcome; Oxygen; Pathology; Pd-porphyrin; Phototoxicity; Physiological; Play; Porphyrins; Positioning Attribute; Production; Property; Proteins; Research; Research Personnel; Role; Route; Sampling; Serum Albumin; Singlet Oxygen; Skeleton; Slice; Solutions; Surface; Techniques; Technology; Temperature; Testing; Thick; Three-Dimensional Image; Three-Dimensional Imaging; Tissues; Toxic effect; Toxicity Tests; Toxicology; Translations; Water; Width; Work; absorption; aqueous; attenuation; base; brain tissue; clinical application; design; functional group; in vivo; luminescence; macromolecule; metal complex; mouse model; nanosensors; novel strategies; phosphorescence; sensor; single molecule; tissue oxygenation; tumor

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 tetrabenzopoiphyrins, 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.

磷光的氧依赖性猝灭是一种灵敏且稳健的测量方法， 分子氧，特别是在体内组织中。已经证明，氧气的3D成像在 当近红外吸收磷光氧 将传感器添加到血液中。我们建议开发适合测量的无毒光学纳米传感器 以及对体内组织微血管中的氧气进行成像，准备用于临床。 我们将合成具有近红外吸收和发射的生物相容性氧纳米传感器 和针对组织中的测量而优化的猝灭常数。磷光体将是多层的，即， 四苯并卟啉的金属络合物，包封在树枝状聚合物内并涂覆有 低聚乙二醇（PEG）。近红外吸收发光金属卟啉将作为 氧气传感器树枝状聚合物将与卟啉共价连接以形成保护壳， 将氧扩散速率调节到组织氧测量的最佳值。树枝状的外壳 还有助于保护卟啉核心不与血液成分相互作用，并将作为清除剂 单线态氧然后，卟啉树枝状聚合物将被靶向用于通过包被来快速排泄（通过肾脏）。 它们的外表面上有聚乙二醇。PEG将使卟啉-树枝状聚合物与其它聚合物的相互作用隔离。 血液成分。因此，传感器发光强度和寿命将变得完全不敏感 环境中的物种而不是氧气。 纳米传感器的急性和长期毒性将在新生仔猪中进行彻底测试 模型和小鼠模型。我们的目标是创建一个纳米传感器的氧气，适用于 临床使用，将其移动到准备好转化为临床的程度，即准备好进行更大规模的应用 合成和严格的毒理学研究准备用于临床试验。