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: 7384375
• 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 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384375
• 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; Compatible; Complex; Dendrimers; Dependency; Development; Diffuse; Diffusion; Disease; Encapsulated; Environment; Evaluation; Excretory function; Family; Freezing; Future; Generations; Goals; Growth; Hypoxia; Image; Imaging technology; In Vitro; Invasive; 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; Rate; 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; size; 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.

氧猝灭磷光是一种灵敏、可靠的测量方法 分子氧，尤其是体内组织中的分子氧。已经证明，氧气的3D成像 当近红外吸收磷光时，可以使用近红外光来完成组织 传感器被添加到血液中。我们建议开发适用于测量的无毒光学纳米传感器 以及体内组织微血管培养中的成像氧气，准备转化为临床。 我们将合成具有近红外吸收和发射功能的生物相容氧纳米传感器 以及最适合在组织中测量的猝灭常数。荧光粉将是多层的，即 四苯并二氮杂菲的金属络合物，包裹在树枝状大分子内，并包覆 低聚乙二醇组分(PEG)。近红外吸收发光的金属卟啉将作为 真正的氧气传感器。树枝状大分子将共价连接到卟啉上，形成保护壳， 将氧气扩散速率调整为组织氧气测量的最佳值。树枝状的贝壳将 也有助于保护卟啉核心不与血液成分相互作用，并将作为清道夫 单线态氧。然后，卟啉树枝状大分子将通过包衣被快速排泄(通过肾脏)。 它们的外表面都有钉子。聚乙二醇乙二醇酯将使卟啉-树枝状大分子与其他化合物相互作用 血液成分。因此，传感器的发光强度和寿命将变得完全不敏感。 对氧气以外的环境中的物种。 纳米传感器的急性和长期毒性将在新生仔猪身上进行详尽的测试。 模型组和小鼠模型组。其目标是创造一种纳米氧气传感器(S)，适用于 临床应用，将其转移到可以转化为临床的点，即准备好更大规模的应用 准备用于临床试验的合成和严格的毒理学研究。