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：
8111827
负责人：
STANISLAV Y EMELIANOV
金额：
$ 32.29万
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/8111827
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）：局部和/或区域性乳腺癌的治愈性治疗需要手术和辅助治疗，例如热疗。在乳腺癌的热处理中，组织暴露在高温下，破坏并杀死癌细胞，同时对正常组织的伤害最小。我们研究计划的总体目标是使用靶向金属纳米颗粒开发一种图像引导的分子特异性光热疗法。具体来说，使用靶向等离子体纳米传感器和先进的体内、非侵入性、功能性、分子特异性成像技术（即集成超声、光声和弹性成像），可以大大改善光热疗法。事实上，在治疗过程之前，使用超声波（解剖和血流成像）和弹性成像（生物力学功能成像），将对肿瘤进行非侵入性成像，以制定适当的治疗计划。此外，分子特异性光吸收剂与癌组织的传递和相互作用将使用光声学进行成像，这是一种能够在足够深度对等离子体纳米粒子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上升来指导光热治疗，从而监测癌症治疗。最后，治疗后，联合成像将用于准确评估短期和长期治疗结果。当前应用的中心主题有三个：开发多功能等离子体纳米颗粒，既可作为光热治疗的光吸收剂，又可作为分子和热成像的造影剂；设计并建造集成超声、光声和弹性成像系统的实验室原型；并初步在 3D 组织模型和小动物癌症模型离体和体内测试所开发的纳米颗粒和成像技术。因此，所有的理论和实验研究都将用于评估分子特异性、图像引导光热疗法治疗癌症的适用性。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：癌症是一种以细胞失控、异常生长为特征的疾病。由此产生的肿瘤可以侵入并破坏周围的健康组织。癌症是美国第二大死因，仅次于心脏病。乳腺癌治疗通常需要手术和热疗等辅助治疗。在乳腺癌的热处理中，组织暴露在高温下，从而破坏并杀死癌细胞，同时对正常组织的伤害最小。癌症热处理的主要目标是选择性地加热少量癌细胞，导致肿瘤坏死，同时保护周围的健康组织。因此，为了成功地进行光热癌症治疗，需要一种能够帮助有效规划、指导和监测光热治疗的成像技术。我们研究项目的总体目标是开发靶向多功能纳米颗粒以及组合超声、光声和弹性成像系统以辅助光热治疗。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，实时成像系统将通过跟踪温度上升和监测癌症治疗来指导光热治疗。最后，治疗后，联合成像将用于准确评估短期和长期治疗结果。