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

金属纳米粒子介导的癌症诊断、靶向和治疗

基本信息

批准号：
8223310
负责人：
James W Tunnell
金额：
$ 29.12万
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：
2008
资助国家：
美国
起止时间：
2008-05-05 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8223310
关键词：
Achievement Adopted Affinity Animal Model Antibodies Architecture Binding Biological Blood Physiology Cell Culture Techniques Cells Characteristics Chemistry Contrast Media Development Diagnosis Diffuse Disease Early Diagnosis Epidermal Growth Factor Receptor Excision Exhibits Gold Heating Image In Vitro Injection of therapeutic agent Injury Kinetics Label Lasers Light Location Malignant Neoplasms Measurement Mediating Mediator of activation protein Metals Methods Modeling Molecular Molecular Models Monitor Mus Nanotechnology Normal Cell Optics Outcome Particle Size Pathology Physiologic pulse Physiology Property Protein Denaturation Proteins Protocols documentation Resolution Shapes Site Spectrum Analysis Staging Structure Surface System Techniques Technology Testing Therapeutic Therapeutic Agents Three-Dimensional Imaging Time Tissues Translations Treatment Protocols absorption base cancer cell cancer imaging cancer therapy cell injury cell killing comparative efficacy design dosage dosimetry imaging modality in vivo irradiation mathematical model minimally invasive molecular dynamics molecular modeling nano nanometer nanoparticle next generation optical fiber optical imaging particle pre-clinical preclinical study response tool tumor

项目摘要

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.

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。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chloroform-enhanced incorporation of hydrophobic gold nanocrystals into dioleoylphosphatidylcholine (DOPC) vesicle membranes.

DOI：
10.1021/la302740j
发表时间：
2012-09-11
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
0
作者：
Rasch MR;Yu Y;Bosoy C;Goodfellow BW;Korgel BA
通讯作者：
Korgel BA

Intra-organ Biodistribution of Gold Nanoparticles Using Intrinsic Two-photon Induced Photoluminescence.

DOI：
10.1002/lsm.20935
发表时间：
2010-09
期刊：
LASERS IN SURGERY AND MEDICINE
影响因子：
2.4
作者：
Park, Jaesook;Estrada, Arnold;Schwartz, Jon A.;Diagaradjane, Parmeswaran;Krishnan, Sunil;Dunn, Andrew K.;Tunnell, James W.
通讯作者：
Tunnell, James W.

Chains, sheets, and droplets: assemblies of hydrophobic gold nanocrystals with saturated phosphatidylcholine lipid and squalene.

链、片和液滴：疏水性金纳米晶体与饱和磷脂酰胆碱脂质和角鲨烯的组装体。