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

描述(申请人提供)：人们普遍认为，癌症管理中能够取得的最大成就是及早发现疾病并随后进行治疗。下一代癌症管理策略将极大地受益于结合早期疾病的成像、靶向和治疗的技术。纳米技术的最新进展已经产生了一类光学活性金属粒子，具有非常理想的分子和光学性质，适合结合这三个方面。它们可以被光学成像，因为它们表现出可调到近红外光谱的强烈光学吸收，而在体内光学成像是最佳的。由于它们是由贵金属制成的，它们在生物上是非活性和无毒的，并且它们具有有利于抗体标记的表面化学物质。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，从而实现光热治疗应用。要成功地将这些纳米颗粒转化为成像、靶向和治疗的组合制剂，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规划。拟议的项目代表了一项长期的跨学科努力，目的是开发一种使用金属纳米颗粒作为介体的癌症成像、靶向和治疗技术。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的位置、组织病理学和治疗反应(目标1)。我们将研究纳米颗粒肿瘤靶向的动力学，并开发有效地将纳米颗粒输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标记肿瘤诱导细胞损伤的最佳激光照射条件。我们的方法包括蛋白质-纳米颗粒相互作用的多尺度分子建模和体外验证(目标3)。该项目的最终结果将在临床前动物模型中证明，在不直接损害邻近正常细胞的情况下，高度选择性地杀死癌细胞(目标4)。从长远来看，这种技术通过在细胞和亚细胞水平选择性地治疗疾病，提供了绕过目前手术切除的限制的可能性。人们普遍认为，癌症管理所能取得的最大成就是及早发现疾病并随后进行治疗。拟议的项目代表了一项跨学科的努力，目的是开发一种使用金属纳米颗粒作为介体的癌症成像、靶向和治疗技术。从长远来看，这种技术通过在细胞和亚细胞水平选择性地治疗疾病，提供了绕过目前手术切除的限制的可能性。人们普遍认为，在癌症管理方面可以取得的最大成就是 疾病的早期发现和随后的治疗。拟议的项目代表着一个 跨学科努力开发一种结合成像、靶向和治疗的技术 使用金属纳米颗粒作为介体的癌症。从长远来看，这样的技术提供了 通过选择性地治疗疾病来绕过目前手术切除的限制的可能性 细胞和亚细胞水平。

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.