DEVELOPMENT OF OPTICAL NANOTHERMOMETERS FOR MEDICAL APPLICATIONS

医疗应用光学纳米温度计的开发

• 批准号: 8054330
• 负责人: Mikhail Y. Berezin
• 金额: $ 16.03万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8054330
• 关键词: Ablation; Adverse effects; Amino Acids; Animals; Applications Grants; Biological Models; Biomedical Technology; Body Temperature; Cell Survival; Cells; Development; Diagnostic; Dyes; Ensure; Excision; Fluorescence; Fluorescent Dyes; Focused Ultrasound Therapy; Foundations; Goals; Gold; Heating; High temperature of physical object; Injury; Lasers; Lead; Life; Light; Longitudinal Studies; Maps; Medical; Methods; Modality; Monitor; Mus; Operative Surgical Procedures; Optics; Organ; Penetration; Physiological; Polyethylene Glycols; Procedures; Process; Property; Prostatic Neoplasms; Radiofrequency Interstitial Ablation; Recurrence; Reporter; Reporting; Risk; Safety; Site; Surface; Temperature; Testing; Thermal Ablation Therapy; Thermometers; Tissues; base; cancer therapy; dosage; fluorophore; improved; in vitro testing; in vivo; light scattering; meetings; microwave electromagnetic radiation; nano; nanoparticle; nanoprobe; novel; prototype; public health relevance; radiofrequency; tumor; tumor eradication

DESCRIPTION (provided by applicant): The thermal ablation of tumors, encompassing laser ablation and focused ultrasound and radiofrequency ablation, is an alternative method to overcome the problems associated with open surgery and is founded on destruction of tumors by applying the heat directly to the tumor site. Thermal treatment of tumors, however, is hindered if the tumor is in close proximity to vital organs sensitive to overheating. On the other hand, over-cautious heating results in incomplete tumor eradication and early tumor recurrences. Therefore, control over the heating process is of critical importance to ensure uniform and adequate heating of the tumor. The development of an optically guided method to control and improve thermal ablation constitutes the overall goal of this project. We propose a method of tumor treatment based on thermal ablation enhanced with temperature sensitive nanoparticles (nanothermometers). The principle of temperature sensitivity of the nanothermometers is based on thermally induced fluorescence. At a normal body temperature, the nanoparticles are invisible; upon heating, the nanoparticles generate fluorescence and become visible. Towards our goal, we will synthesize different nanoparticles and optimize their properties. The temperature sensitive nanoparticles will be constructed from non-toxic materials such as gold, near infrared dyes frequently used in diagnostics, and linkers composed from common amino acids or polyethylene glycols. The nanoparticles will be rigorously tested in vitro, in cells, phantoms and in small animals. In the conclusion of the study, the nanoparticles will be delivered to the tumor site and the tumor will be exposed to the thermal energy. We will be using laser ablation as a method of choice for delivering thermal energy. Under laser ablation conditions, the proposed nanoparticles will provide three important functions: i they will report and control the heating process by turning fluorescence "ON" at the desired temperature, ii they will convert light energy to heat, increasing the temperature inside the tumor, and iii they will propagate energy deep into the tumor, thus providing uniform heating. We expect to establish a strong foundation for utilizing thermal ablation in combination with temperature sensitive nanoparticles in the treatment of tumors. The development of such novel biomedical technology would represent a significant advancement in the treatment of cancer. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop an optically guided thermal ablation method for treatment of tumors using nanothermometers to ensure both uniform and adequate heating of the tumors. These nanothermometers will allow for a higher level of control over the ablation procedure and render the treatment of tumors safer by lowering the chances of tumor recurrences.

描述（由申请人提供）：肿瘤的热消融，包括激光消融、聚焦超声和射频消融，是克服开放手术相关问题的替代方法，其基础是通过将热量直接施加到肿瘤部位来破坏肿瘤。然而，如果肿瘤非常接近对过热敏感的重要器官，则肿瘤的热治疗会受到阻碍。另一方面，过于谨慎的加热会导致肿瘤根除不彻底和早期肿瘤复发。因此，对加热过程的控制对于确保肿瘤的均匀和充分加热至关重要。开发一种光学引导的方法来控制和改善热消融构成了该项目的总体目标。 我们提出了一种基于温度敏感纳米颗粒（纳米温度计）增强的热消融的肿瘤治疗方法。纳米温度计的温度灵敏度的原理是基于热诱导荧光。在正常体温下，纳米颗粒是不可见的;加热后，纳米颗粒产生荧光并变得可见。为了实现我们的目标，我们将合成不同的纳米粒子并优化其性能。温度敏感纳米颗粒将由无毒材料构建，例如金，诊断中常用的近红外染料，以及由常见氨基酸或聚乙二醇组成的连接剂。纳米粒子将在体外、细胞、体模和小动物中进行严格的测试。在研究结束时，纳米颗粒将被递送到肿瘤部位，肿瘤将暴露于热能。我们将使用激光烧蚀作为传递热能的首选方法。在激光消融条件下，所提出的纳米颗粒将提供三个重要功能：i它们将通过在所需温度下将荧光“打开”来报告和控制加热过程，ii它们将光能转化为热量，增加肿瘤内部的温度，以及iii它们将能量传播到肿瘤深处，从而提供均匀加热。我们期望为热消融结合温度敏感纳米颗粒治疗肿瘤奠定坚实的基础。这种新型生物医学技术的发展将代表癌症治疗的重大进步。 公共卫生相关性：该项目的目标是开发一种光学引导的热消融方法，用于使用纳米温度计治疗肿瘤，以确保肿瘤的均匀和充分加热。这些纳米温度计将允许对消融过程进行更高水平的控制，并通过降低肿瘤复发的机会使肿瘤治疗更安全。

项目成果

Design of fluorescent nanocapsules as ratiometric nanothermometers.

• DOI: 10.1002/chem.201402828
• 发表时间: 2014-08-11
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Zhegalova NG;Dergunov SA;Wang ST;Pinkhassik E;Berezin MY
• 通讯作者: Berezin MY

Dating bloodstains with fluorescence lifetime measurements.

• DOI: 10.1002/chem.201102935
• 发表时间: 2012-01-27
• 期刊: CHEMISTRY-A EUROPEAN JOURNAL
• 影响因子: 4.3
• 作者: Guo, Kevin;Achilefu, Samuel;Berezin, Mikhail Y.
• 通讯作者: Berezin, Mikhail Y.

Design of irreversible optical nanothermometers for thermal ablations.

• DOI: 10.1039/c2cc37271a
• 发表时间: 2013-01-25
• 期刊: Chemical communications (Cambridge, England)
• 作者: Gustafson TP;Cao Q;Wang ST;Berezin MY
• 通讯作者: Berezin MY

BLOOD TRIGGERED RAPID RELEASE POROUS NANOCAPSULES.

• DOI: 10.1039/c3ra22693j
• 发表时间: 2013-01-24
• 期刊: RSC advances
• 影响因子: 3.9
• 作者: Gustafson TP;Dergunov SA;Akers WJ;Cao Q;Magalotti S;Achilefu S;Pinkhassik E;Berezin MY
• 通讯作者: Berezin MY

Minimization of self-quenching fluorescence on dyes conjugated to biomolecules with multiple labeling sites via asymmetrically charged NIR fluorophores.

• DOI: 10.1002/cmmi.1585
• 发表时间: 2014-09
• 期刊: CONTRAST MEDIA & MOLECULAR IMAGING
• 作者: Zhegalova, Natalia G.;He, Shawn;Zhou, Haiying;Kim, David M.;Berezin, Mikhail Y.
• 通讯作者: Berezin, Mikhail Y.