Metal nanoparticle-mediated diagnosis, targeting, and treatment of cancer

描述（由申请人提供）：人们普遍认为癌症管理的最大成就是疾病的早期发现和后续治疗。下一代癌症管理策略将极大地受益于结合成像、靶向和早期疾病治疗的技术。纳米技术的最新进展已经产生了一类具有光学活性的金属颗粒，它们具有非常理想的分子和光学性质，适合于将这三个方面结合起来。它们可以进行光学成像，因为它们表现出很强的光学吸收，可调到近红外光谱，在体内光学成像是最佳的。由于它们是由贵金属制成的，因此它们具有生物无反应性和无毒性，并且它们具有有利于抗体标记的表面化学成分。它们的金属结构非常稳定，可以有效地将吸收的光转化为热，从而实现光热治疗的应用。成功地将这些纳米颗粒转化为成像、靶向和治疗剂，需要开发非侵入性成像策略、体内细胞特异性靶向方案和最佳剂量计划。拟议的项目代表了一项长期的跨学科努力，以开发一种结合成像、靶向和治疗癌症的技术，使用金属纳米颗粒作为介质。拟议的研究将开发微创光学成像和传感工具，用于定量评估纳米颗粒位置、组织病理和治疗反应（目的1）。我们将研究纳米颗粒靶向肿瘤的动力学，并制定有效将纳米颗粒递送到肿瘤部位的策略（目标2）。我们将在单细胞水平上确定纳米颗粒标记肿瘤诱导细胞损伤的最佳激光照射。我们的方法包括蛋白质-纳米颗粒相互作用的多尺度分子模型和体外验证（目标3）。该项目的最终结果将在临床前动物模型中证明高度选择性的癌细胞杀死而不损害立即邻近的正常细胞（目标4）。从长远来看，这些技术通过在细胞和亚细胞水平上选择性治疗疾病，提供了规避目前手术切除限制的可能性。人们普遍认为，在癌症管理中可以取得的最大成就是疾病的早期发现和后续治疗。拟议的项目代表了跨学科的努力，以开发一种结合成像、靶向和治疗癌症的技术，使用金属纳米颗粒作为介质。从长远来看，这些技术通过在细胞和亚细胞水平上选择性治疗疾病，提供了规避目前手术切除限制的可能性。人们普遍认为，在癌症管理中所能取得的最大成就是

DESCRIPTION (provided by applicant): It is widely believed that the greatest achievement that can be made in cancer management is the early detection and subsequent treatment of disease. The next generation cancer management strategies will greatly benefit from technologies that combine imaging, targeting, and treating of the earliest stage disease. Recent advances in nanotechnologies have produced a class of optically active metal particles with highly desirable molecular and optical properties suitable for combining these three aspects. They can be imaged optically as they exhibit strong optical absorption that is tunable to the near infrared spectrum where in vivo optical imaging is optimum. As they are fabricated from noble metals, they are biologically non-reactive and non- toxic, and they have surface chemistries that are conducive to antibody labeling. Their metal structure is extremely stable and efficiently converts absorbed light to heat, allowing for photothermal therapeutic applications. Successful translation of these nanoparticles as combined imaging, targeting, and therapeutic agents requires the development of non-invasive imaging strategies, in vivo cell specific targeting protocols, and optimum dosimetry planning. The proposed project represents a long term interdisciplinary effort to develop a technology combining imaging, targeting, and treatment of cancer using metal nanoparticles as the mediator. The proposed studies will develop minimally invasive optical imaging and sensing tools for quantitative assessment of nanoparticle location, tissue pathology, and therapeutic response (Aim 1). We will investigate the kinetics of nanoparticle tumor targeting and develop strategies for efficient delivery nanoparticles to the tumor site (Aim 2). We will determine the optimum laser irradiation of the nanoparticle labeled tumor to induce cell injury at the single cell level. Our approach includes multiscale molecular modeling of protein-nanoparticle interactions and in vitro verification (Aim 3). The final outcome of this project will demonstrate in a preclinical animal model highly selective cancer cell killing without damaging immediately adjacent normal cells (Aim 4). In the long term, such technologies offer the possibility to circumvent current limitations of surgical removal by selectively treating disease at the cellular and sub-cellular level. It is widely believed that the greatest achievement that can be made in cancer management is the early detection and subsequent treatment of disease. The proposed project represents an interdisciplinary effort to develop a technology combining imaging, targeting, and treatment of cancer using metal nanoparticles as the mediator. In the long term, such technologies offer the possibility to circumvent current limitations of surgical removal by selectively treating disease at the cellular and sub-cellular level. It is widely believed that the greatest achievement that can be made in cancer management is the early detection and subsequent treatment of disease. The proposed project represents an interdisciplinary effort to develop a technology combining imaging, targeting, and treatment of cancer using metal nanoparticles as the mediator. In the long term, such technologies offer the possibility to circumvent current limitations of surgical removal by selectively treating disease at the cellular and sub-cellular level.