Molecular photothermal therapy of cancer using targeted metal nanoparticles

描述(由申请人提供)： 局部和/或区域性乳腺癌的根治治疗需要手术和辅助治疗，如热疗。在乳腺癌的热疗中，组织暴露在高温下，破坏和杀死癌细胞，对正常组织的伤害最小。我们研究计划的总体目标是开发一种使用靶向金属纳米颗粒的图像引导的、分子特异性的癌症光热疗法。具体地说，使用靶向等离子体纳米传感器和先进的在体、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)，可以极大地改进光热治疗。事实上，在治疗程序之前，使用超声(解剖和血流成像)和弹性成像(生物机械功能成像)，将对肿瘤进行非侵入性成像，以制定适当的治疗计划。此外，分子特定的光吸收剂与癌症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颗粒进行体内成像的技术。在治疗期间，实时成像系统将被用来通过跟踪温度上升来指导光热治疗，从而监测癌症的治疗。最后，在治疗后，将使用联合成像来准确评估短期和长期治疗结果。目前应用的中心主题是三个方面：开发多功能等离子体纳米颗粒，既作为光热治疗的光吸收剂，又作为分子和热成像的造影剂；设计和建造集成超声、光声和弹性成像系统的实验室原型；以及在体内外三维组织模型和小动物癌症模型中初步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被用来评估分子特异性的、图像引导的光热疗法在治疗癌症方面的适用性。在研究的最后，我们将概述临床影像引导光热疗法系统的设计和技术指标。

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.