Optoacoustic system for monitoring biodistribution of nanoparticles in vivo.

用于监测体内纳米颗粒生物分布的光声系统。

• 批准号: 8203540
• 负责人: ALEXANDER A ORAEVSKY
• 金额: $ 11.51万
• 依托单位: TOMOWAVE LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8203540
• 关键词: Adverse effects; Animals; Area; Biocompatible; Biodistribution; Biological; Biomedical Engineering; Blood; Blood specimen; Businesses; Carbon; Carbon Nanotubes; Complex; Computers; Data; Detection; Development; Devices; Dimensions; Disease; Drug Kinetics; Engineering; Exhibits; Fluorescence Spectroscopy; Future; Gold; Harvest; Health; Image; Imaging technology; Kidney; Kinetics; Laboratories; Lasers; Lead; Life; Liver; Magnetic Resonance Imaging; Measurement; Measures; Metabolic Clearance Rate; Methods; Monitor; Mus; Nanotechnology; Optics; Organ; Organ Harvestings; Organism; Pharmaceutical Preparations; Phase; Polyethylene Glycols; Process; Qualifying; Reproducibility; Research; Research Personnel; Resolution; Risk; Risk Assessment; Safety; Sampling; Sensitivity and Specificity; Signal Transduction; Specificity; Speed; Spleen; System; Technology; Therapeutic; Therapeutic procedure; Time; Time Study; Tissues; Translating; Ultrasonography; Variant; Vascular System; Work; absorption; base; cancer therapy; clinical practice; commercialization; cost; empowered; imaging modality; improved; in vivo; instrumentation; interest; intravenous administration; nano; nanodevice; nanodrug; nanoparticle; nanorod; new technology; non-invasive monitor; novel; pre-clinical research; prototype; single walled carbon nanotube; tomography

DESCRIPTION (provided by applicant): We propose novel application of optoacoustic tomography for non-invasive and quantitative analysis of nanoparticle biodistribution in preclinical research. Novel nanotechnology-based treatments of cancer and other diseases with increased specificity and enhanced therapeutic potential are being actively developed at present. There is a pressing need for low-cost and high-sensitivity instrumentation capable of monitoring proliferation and clearance of nanoparticles in vivo to perform health safety assessments and determine efficacy of disease treatments. Current non-invasive methods of nanoparticle detection, such as magnetic resonance imaging and radiological imaging (i.e. computer tomography and its variants) remain expensive and are not accessible to many businesses involved in advancing nanotechnology-based drugs and therapeutic strategies in clinical practice. Instead, tedious post-mortem analysis of numerous samples remains a common method to perform nanoparticle biodistribution studies. Optoacoustic tomography is a novel imaging technology based on optical absorptivity of tissues and high resolution of ultrasound to produce three-dimensional images of vasculature and internal organs in small animals. Since a wide variety of gold and carbon-based nanoparticles, as well as select biodegradable nano- complexes already exhibit or can be engineered to display strong optical resonances in a near-infrared spectral region, a so-called biological transparency window, their small quantities can be detected in vivo with optoacoustics. In this work, we propose to demonstrate feasibility of using optoacoustic technology to perform quantitative biodistribution analysis of gold nanorods and carbon nanotubes in mice. Our optoacoustic tomography system will detect small volumetric changes in absoprtivity corresponding to less than 1 % of an organ absorbance at a specific wavelength. We propose to establish a correlation between absorption increase and a concentration of nanoparticles in a particular organ to allow quantitative measurements of nanoparticles in vivo. This will allow us to define sensitivity limits of our method and demonstrate its benefits in terms of cost, versatility, sensitivity and resolution and assess its potential for a future commercialization. The PI is an internationally recognized leader in optoacoustic imaging technology and its commercialization and will guide the team of highly qualified experts in nanotechnology and optoacoustic tomography towards successful completion of a project. The proposed technology will lead towards commercial instrumentation that will provide a significantly cheaper, safer and more versatile alternative to current non invasive imaging modalities, such as CT and MRI. Our imaging system will have a high demand in a nanotechnology-oriented bioengineering businesses and academic circles with applications in pharmacokinetics analysis, biodistribution studies and health risk assessments of novel nano-drugs and nano-devices. PUBLIC HEALTH RELEVANCE: Efficient and affordable imaging technologies capable of non-invasive and highly sensitive imaging of nanoparticles in vivo are needed to perform health risk assessment and biodistribution analysis of nanoparticles and novel nanotechnology-based drugs. Here we demonstrate that optoacoustic tomography is capable of detecting small quantities of carbon and gold nanoparticles and monitor their proliferation in vivo. We propose to define sensitivity of optoacoustic tomography and calibrate the imaging system to allow quantitave measurements of nanoparticle concentrations directly in small animals. Novel, inexpensive and reliable imaging modality is proposed to empower businesses and non-profit researchers interested in developing nanotechnology-based drugs and disease treatments, analyzing health risks presented by nanoparticles and developing strategies to reduce adverse effects associated with nanoparticle presence.

描述（由申请人提供）：我们提出了光声断层扫描的新颖应用，用于临床前研究中纳米粒子生物分布的非侵入性和定量分析。目前正在积极发展基于纳米技术的新型癌症和其他具有提高特异性和增强治疗潜力的疾病的治疗方法。迫切需要低成本和高敏化仪器能够监测体内纳米颗粒的增殖和清除，以进行健康安全评估并确定疾病治疗的功效。纳米颗粒检测的当前非侵入性方法，例如磁共振成像和放射学成像（即计算机断层扫描及其变体）仍然昂贵，并且许多涉及促进纳米技术药物和临床实践中基于纳米技术的药物和治疗策略的企业无法使用。取而代之的是，对众多样本进行繁琐的验尸分析仍然是执行纳米颗粒生物分布研究的常见方法。 光声断层扫描是一种基于组织的光吸收性和超声波的高分辨率，在小动物中产生脉管系统和内部器官的三维图像。由于各种黄金和碳基的纳米颗粒以及精选的可生物降解纳米络合物已​​经表现出来，也可以设计以在近红外光谱区域显示强烈的光学共振，因此可以在OptoAcousics中在Vivo中检测到所谓的生物透明度窗口。在这项工作中，我们建议证明使用光声技术对小鼠的金纳米棒和碳纳米管进行定量生物分布分析。我们的光声断层扫描系统将检测到对应于特定波长下的器官吸光度不到1％的吸收性变化。我们建议在特定器官中建立吸收增加与纳米颗粒浓度之间的相关性，以允许对体内的纳米颗粒进行定量测量。这将使我们能够定义方法的灵敏度限制，并在成本，多功能性，敏感性和解决方案方面证明其优势，并评估其未来商业化的潜力。 PI是光气成像技术及其商业化的国际认可的领导者，将指导纳米技术和光声断层扫描方面的高素质专家团队成功完成项目。拟议的技术将导致商业仪器，该工具将为当前非侵入性成像方式（例如CT和MRI）提供更便宜，更安全，更广泛的替代品。我们的成像系统将对以纳米技术为导向的生物工程企业和学术界有很高的需求，并在药代动力学分析，生物分布研究和对新型纳米药物和纳米devices的健康风险评估中进行了应用。 公共卫生相关性：需要在体内对纳米颗粒进行非侵入性和高度敏感成像的高效成像技术，以对纳米颗粒和新型纳米技术药物进行健康风险评估和生物分布分析。在这里，我们证明了光声断层扫描能够检测少量的碳和金纳米颗粒并监测其体内的增殖。我们建议定义光声断层扫描的灵敏度并校准成像系统，以允许直接在小动物中的纳米颗粒浓度进行定量测量。提出了新颖，廉价且可靠的成像方式，以增强业务和非营利性研究人员的能力，并有兴趣开发纳米技术的药物和疾病治疗，分析纳米颗粒提出的健康风险，并制定策略以减少与纳米颗粒存在相关的不良影响。