Development of spin probes for cell-tagging and oximetry

开发用于细胞标记和血氧测定的自旋探针

• 批准号: 7590766
• 负责人: PERIANNAN KUPPUSAMY
• 金额: $ 33.75万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7590766
• 关键词: Affect; Animal Disease Models; Animal Model; Be++ element; Beryllium; Biochemical Process; Biocompatible; Biological; Cell Respiration; Cells; Cessation of life; Class; Clinical; Cutaneous; Development; Devices; Dimensions; Electron Spin Resonance Spectroscopy; Electron Transport; Encapsulated; Ensure; Evaluation; Family suidae; Functional disorder; Funding; Gases; Growth; Homeostasis; Implant; Invasive; Lead; Life; Malignant Neoplasms; Measurement; Metabolic; Metabolic Diseases; Methodology; Methods; Mitochondria; Monitor; Mus; Muscular Atrophy; Numbers; Organism; Oxygen; Oxygen saturation measurement; Particulate; Pathogenesis; Performance; Peripheral Vascular Diseases; Peripheral arterial disease; Physiology; Play; Process; Radiation therapy; Rattus; Resolution; Role; Safety; Shapes; Site; Standards of Weights and Measures; Sterilization for infection control; Sus scrofa; System; Testing; Tissues; Toxic effect; Toxicology; Tumor Tissue; United States Food and Drug Administration; Validation; Wound Healing; base; biocompatible polymer; biomaterial compatibility; chemical stability; clinical application; clinically relevant; design; human disease; implantation; in vivo; interest; irradiation; polydimethylsiloxane; response; size; tissue oxygenation; tumor

DESCRIPTION (provided by applicant): Oxygen is one of the most important molecules in biological systems since it is involved as either a reactant or a product in a vast number of biochemical processes. The element is found in most biomolecules that are essential to living organisms, and plays a crucial role in cellular respiration and the electron transport chain in the mitochondria of living cells. Any imbalance in oxygen levels, which can occur due to altered supply or utilization of oxygen, may affect metabolic homeostasis and lead to pathophysiology. Thus, a means by which to evaluate and track changes in tissue oxygen levels will be of paramount importance in our ability to understand the mechanisms of pathogenesis and to develop effective strategies to correct the imbalance. This would require methods capable of quantifying the levels of tissue oxygenation with good spatial and temporal resolution. Ideally, these measurements should be obtained through minimally invasive or noninvasive means. Thus, the overall objective of this proposal is to develop safe, implantable oxygen-sensing probes (OxyChips) for electron paramagnetic resonance (EPR) oximetry that can be used in clinical applications. The probes will be designed to be implanted in the tissue of interest, permitting repeated measurements of tissue oxygenation from the same site by noninvasive means. This new class of EPR probes will be based on oxygen-sensitive particulate probes embedded in an oxygen-permeable biocompatible substrate, polydimethylsiloxane (PDMS). Using this approach, OxyChip implants of various shapes, sizes, and dimensions will be fabricated and characterized. The robustness of the probes will also be tested to ensure that they will perform as expected. Biocompatibility testing and validation of the probe applicability will then be performed in several clinically-relevant animal models of human disease. The following specific aims are proposed: 1) Encapsulation of particulate EPR probes and fabrication of OxyChips; 2) Biostability and biocompatibility evaluation of encapsulated EPR particulates; 3) Toxicity, immunological response, and safety evaluation of OxyChips, and 4) In vivo implantation and testing of OxyChips in clinically-relevant animal models of disease. The information gained from these devices will provide a better understanding of various metabolic and disease states (e.g. cancer and peripheral vascular disease) and help in making effective clinical decisions regarding treatment and therapy. The long-term objective of this proposal is to develop implantable, oxygen-sensing probes for use in clinical electron paramagnetic resonance (EPR) oximetry. Oxygen is found in most biomolecules that are essential to living organisms, and plays a role in a number of processes in both normal and altered physiology. Once implanted, the new probes will permit repeated, noninvasive measurement of oxygen concentration in tissues. The probes could be used to track growth and/or death of tumor tissues, progression of peripheral arterial disease and muscular atrophy, and wound healing response.

描述(申请人提供)：氧是生物系统中最重要的分子之一，因为它在大量的生化过程中要么作为反应物要么作为产物。这种元素存在于大多数生命有机体所必需的生物分子中，在细胞呼吸和活细胞线粒体的电子传输链中起着至关重要的作用。由于氧的供应或利用的改变而导致的氧水平的任何失衡，都可能影响代谢稳态，并导致病理生理学。因此，一种评估和跟踪组织氧水平变化的方法对于我们理解发病机制和制定有效的纠正失衡的策略将是至关重要的。这将需要能够以良好的空间和时间分辨率量化组织氧合水平的方法。理想情况下，这些测量应该通过微创或非侵入性手段获得。因此，这项建议的总体目标是开发安全的、可植入的氧敏探针(OxyChips)，用于电子顺磁共振(EPR)血氧测定，可用于临床应用。这些探头将被设计成植入感兴趣的组织，允许通过非侵入性手段从同一位置重复测量组织氧合。这种新型的EPR探测器将基于嵌入在透氧性生物兼容底物聚二甲基硅氧烷(PDMS)中的氧敏感颗粒探测器。使用这种方法，将制造不同形状、大小和尺寸的OxyChip植入物并对其进行表征。还将测试探测器的健壮性，以确保它们将按预期运行。然后，将在几个临床相关的人类疾病动物模型中进行生物兼容性测试和探头适用性的验证。提出了以下具体目标：1)微粒型EPR探针的包裹和OxyChips的制备；2)包裹型EPR微粒的生物稳定性和生物相容性评价；3)OxyChips的毒性、免疫学反应和安全性评价；4)OxyChips在临床相关动物模型中的体内植入和测试。从这些设备获得的信息将提供对各种代谢和疾病状态(例如癌症和外周血管疾病)的更好了解，并有助于做出关于治疗和治疗的有效临床决策。这项提议的长期目标是开发用于临床电子顺磁共振(EPR)血氧仪的植入式氧气传感探针。氧存在于生命有机体所必需的大多数生物分子中，在正常和改变的生理过程中都发挥着作用。一旦植入，新的探针将允许重复、非侵入性地测量组织中的氧浓度。该探针可用于跟踪肿瘤组织的生长和/或死亡、外周动脉疾病和肌肉萎缩的进展以及伤口愈合反应。