Molecular photothermal therapy of cancer using targeted metal nanoparticles

使用靶向金属纳米粒子的癌症分子光热疗法

基本信息

批准号：
8267111
负责人：
STANISLAV Y EMELIANOV
金额：
$ 30.84万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8267111
关键词：
3-Dimensional Acoustics Address Adjuvant Therapy Algorithms Amplifiers Animal Cancer Model Binding Biological Markers Biomechanics Biomedical Engineering Blood flow Breast Cancer Treatment Cancerous Cause of Death Cells Clinical Color Computer software Contrast Media Custom Diagnosis Disease Elasticity Elements Ensure Epidermal Growth Factor Receptor Fiber Frequencies Functional Imaging Goals Gold Heart Diseases Heating High temperature of physical object Human Human Characteristics Image Imaging Techniques Imaging technology Indocyanine Green Induced Hyperthermia Injury Invaded Label Laboratories Lasers Lesion Light Living Arrangement Malignant Neoplasms Mammary Gland Parenchyma Mammary Neoplasms Measures Mechanics Mediating Memory Metals Molecular Monitor Monoclonal Antibodies Necrosis Normal tissue morphology Operative Surgical Procedures Optics Outcome Physiologic pulse Physiological Process Property Research Resolution Roche brand of trastuzumab Scanning Shapes Site Slide System Techniques Temperature Testing Theoretical Studies Therapeutic Therapeutic procedure Time Tissue Model Tissue Sample Tissues Transducers Treatment outcome Tumor Tissue Ultrasonics Ultrasonography United States Work base biomaterial compatibility cancer cell cancer therapy cell growth clinically relevant computerized data processing design detector image processing improved in vivo intravenous injection irradiation killings malignant breast neoplasm mouse model nanoparticle nanorod nanosecond nanosensors overexpression particle performance tests plasmonics programs prototype public health relevance research study response success therapy outcome tissue phantom treatment planning tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Curative treatment of local and/or regional breast cancer requires surgery and adjuvant therapy such as thermotherapy. In thermal treatment of breast cancer, the tissue is exposed to high temperatures that damage and kill cancer cells with minimal injury to normal tissues. The overall goal of our research program is to develop an image-guided, molecular specific photothermal therapy of cancer using targeted metal nanoparticles. Specifically, using targeted plasmonic nanosensors and an advanced, in-vivo, noninvasive, functional, molecular specific imaging technology (i.e., integrated ultrasound, photoacoustic and elasticity imaging), photothermal therapy can be greatly improved. Indeed, before the therapeutic procedure, using ultrasound (anatomical and blood flow imaging) and elastography (biomechanical functional imaging), the tumor will be non-invasively imaged to develop an appropriate treatment plan. Furthermore, the delivery and interaction of molecular specific photoabsorbers with cancerous tissue will be imaged using photoacoustics - a technique capable of in-vivo imaging of plasmonic nanoparticles at sufficient depth. During the therapy, the real-time imaging system will be used to guide photothermal therapy by tracking the temperature rise and, therefore, monitoring cancer treatment. Finally, after the therapy, the combined imaging will be used to accurately assess the short-term and the long-term treatment outcome. The central theme of the current application is threefold: to develop multifunctional plasmonic nanoparticles acting as both photoabsorbers for photothermal therapy and contrast agent for molecular and thermal imaging; to design and build a laboratory prototype of the integrated ultrasound, photoacoustic and elasticity imaging system; and to initially test the developed nanoparticles and imaging technology in 3-D tissue phantoms and small animal cancer model ex vivo and in vivo. Therefore, all theoretical and experimental studies will be conducted to evaluate the applicability of the molecular specific, image-guided photothermal therapy to treat cancer. At the end of the study, we will outline the design and technical specifications of a clinical image- guided photothermal therapy system. PUBLIC HEALTH RELEVANCE: Cancer is a disease characterized by uncontrollable, abnormal growth of cells. The resulting tumor can invade and destroy the surrounding healthy tissue. Cancer is the second leading cause of death in the United States, exceeded only by heart disease. Breast cancer treatment often requires surgery and adjuvant therapy such as thermotherapy. In thermal treatment of breast cancer the tissue is exposed to high temperatures that damage and kill cancer cells with minimal injury to normal tissues. The primary goal of thermal treatment of cancer is to selectively heat a small volume of cancerous cells leading to tumor necrosis while protecting the surrounding healthy tissue. Thus, to successfully perform photothermal cancer therapy, an imaging technique that can help effectively plan, guide and monitor the photothermal therapy is needed. The overall goal of our research program is to develop the targeted multifunctional nanoparticles and the combined ultrasound, photoacoustic and elasticity imaging system to assist photothermal therapy. Before the therapeutic procedure, the tumor will be non-invasively imaged to develop an appropriate treatment plan. During the therapy, the real-time imaging system will be used to guide photothermal therapy by tracking the temperature rise and monitoring the cancer treatment. Finally, after the therapy, the combined imaging will be used to accurately assess the short-term and the long-term treatment outcome.

描述（由申请人提供）：治疗局部和/或区域乳腺癌需要手术和辅助治疗，例如热疗。在乳腺癌的热治疗中，组织暴露于高温下，损害正常组织的损伤并杀死癌细胞。我们的研究计划的总体目标是使用靶向金属纳米颗粒开发出癌症的图像引导，分子特异性光热治疗。具体而言，使用靶向的等离子纳米传感器和先进的，体内的，非侵入性，功能性，分子特异性成像技术（即综合超声，光声和弹性成像），可以极大地改进光热疗法。实际上，在治疗过程之前，使用超声（解剖学和血流成像）和弹性图（生物力学功能成像），肿瘤将非侵入性地成像以制定适当的治疗计划。此外，将使用光声学成像分子特异性光吸光器与癌组织的递送和相互作用 - 一种能够在足够深度的等离子体纳米颗粒进行体内成像的技术。在治疗过程中，实时成像系统将用于通过跟踪温度升高并因此监测癌症治疗来指导光热治疗。最后，在治疗后，将使用组合成像来准确评估短期和长期治疗结果。当前应用的中心主题是三倍：开发多功能等离子体纳米颗粒，既充当光热疗法的光吸光器，又是分子和热成像的对比剂；设计和构建集成超声，光声和弹性成像系统的实验室原型；并最初在3-D组织幻象和小动物癌模型和体内测试开发的纳米颗粒和成像技术。因此，将进行所有理论和实验研究，以评估分子特异性，图像引导的光热治疗以治疗癌症的适用性。在研究结束时，我们将概述临床图像引导光热治疗系统的设计和技术规格。公共卫生相关性：癌症是一种以无法控制的细胞生长异常生长为特征。所得的肿瘤可以侵入和破坏周围的健康组织。癌症是美国第二大死亡原因，仅因心脏病而超过。乳腺癌治疗通常需要手术和辅助治疗，例如热疗。在对乳腺癌的热处理中，组织暴露于高温下，损害正常组织的损伤并杀死癌细胞。癌症热治疗的主要目的是选择性加热一小部分的癌细胞，导致肿瘤坏死，同时保护周围的健康组织。因此，为了成功进行光热癌疗法，需要有助于有效计划，指导和监测光热疗法的成像技术。我们的研究计划的总体目标是开发靶向的多功能纳米颗粒以及联合超声，光声和弹性成像系统，以帮助光热治疗。在治疗程序之前，将对肿瘤进行非侵入性成像以制定适当的治疗计划。在治疗过程中，实时成像系统将用于通过跟踪温度升高和监测癌症治疗来指导光热疗法。最后，在治疗后，将使用组合成像来准确评估短期和长期治疗结果。