Biodegradable Plasmonic Nanoparticles for Cancer Imaging and Therapy

用于癌症成像和治疗的可生物降解的等离子体纳米颗粒

• 批准号: 8404023
• 负责人: Konstantin V Sokolov
• 金额: $ 28.27万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8404023
• 关键词: Adsorption; Animals; Architecture; Area; Avidity; Biodegradation; Biodistribution; Biological; Biological Assay; Biological Markers; Biomedical Engineering; Caliber; Cancerous; Cells; Charge; Cluster Analysis; Colloids; Coupled; Data; Detection; Development; Diagnosis; Disease; Drug Formulations; Endocytosis; Environment; Evaluation; Excretory function; Exhibits; Extinction (Psychology); Feces; Goals; Gold; Growth; Hybrids; Image; Image Enhancement; In Vitro; Individual; Injection of therapeutic agent; International; Investigation; Legal patent; Length; Life; Ligands; Link; Longitudinal Studies; Magnetic Resonance Imaging; Malignant Neoplasms; Manuscripts; Mass Spectrum Analysis; Measurement; Mediating; Medical; Metabolic; Metabolic Clearance Rate; Metals; Methodology; Methods; Modeling; Modern Medicine; Molecular; Molecular Target; Monitor; Nanotechnology; Nature; Near-Infrared Spectroscopy; Optics; Organ; Pathology; Pathway interactions; Peptide antibodies; Physiological; Plasma; Polymers; Porosity; Preparation; Procedures; Process; Property; Publishing; Quantum Dots; Research; Roentgen Rays; Route; Scanning Electron Microscopy; Science; Shapes; Signal Transduction; Silver; Site; Slice; Solutions; Solvents; Specificity; Surface; Testing; Therapeutic; Time; Tissue Sample; Tissues; Toxic effect; Translations; Transmission Electron Microscopy; Urine; Validation; Work; absorption; acoustic imaging; base; biodegradable polymer; bioimaging; cancer cell; cancer imaging; cancer therapy; carcinogenesis; cellular imaging; clinical practice; design; evaporation; experience; in vivo; interest; intermolecular interaction; iron oxide; light scattering; macrophage; malignant mouth neoplasm; meetings; member; nanocage; nanocomposite; nanomaterials; nanoparticle; nanorod; nanoshell; novel; optical imaging; particle; photoacoustic imaging; plasmonics; programs; public health relevance; simulation; skills; soft tissue; targeted delivery; time use; tumor; urinary; zeta potential

DESCRIPTION (provided by applicant): It has been convincingly shown that nanotechnology can provide unique solutions to revolutionize diagnosis and treatment of many devastating diseases such as cancer. One specific area of great interest is development of nanoparticles for molecular specific imaging, therapy and combined imaging/therapy. A major roadblock in translation of inorganic nanoparticles to clinical practice for systemic targeting of cancer cells is their non-biodegradable nature. In addition, sizes of coated nanoparticles that are used in biological applications are not small enough to be easily cleared from the body. The accumulation and resulting long- term toxicity of nanoparticles is a major concern. In this research program we will create a new class of biodegradable gold nanoparticles with plasmon resonances in the NIR region. The nanoparticles will degrade to easily clearable components in the body and, therefore, will provide a crucial missing link between the enormous potential of metal nanoparticles for cancer imaging and therapy and translation into clinical practice. Our synthetic methodology is based on controlled assembly of very small (less than 5 nm) primary gold particles into nanoclusters with <100 nm overall diameter and an intense NIR absorbance. The assembly will be mediated by biodegradable polymers and small capping ligands on the primary nanoparticles. After delivery into the body the nanoclusters will biodegrade over time into sub-6 nm ligand capped primary gold nanoparticles, which will be highly favorable for rapid clearance from the body. This hybrid polymer/inorganic material will combine advantages of biodegradability of polymer nanoparticles and strong imaging contrast and therapeutic capabilities afforded by metal nanoparticles. Whereas these nanoclusters will be shown to have widespread potential in imaging/therapy, we will develop and optimize in this particular application biodegradable plasmonic nanoclusters with intense NIR absorbance for photo-acoustic imaging (PA) of cancerous cells. The nanoclusters will be evaluated in biologically relevant models of oral cancer.

描述（由申请人提供）：已经令人信服地表明，纳米技术可以提供独特的解决方案，彻底改变许多破坏性疾病（例如癌症）的诊断和治疗。人们非常感兴趣的一个特定领域是用于分子特异性成像、治疗和组合成像/治疗的纳米颗粒的开发。将无机纳米粒子转化为全身靶向癌细胞的临床实践的主要障碍是其不可生物降解的性质。此外，用于生物应用的涂层纳米颗粒的尺寸不够小，无法轻易从体内清除。纳米粒子的积累和由此产生的长期毒性是一个主要问题。在这个研究项目中，我们将创建一种新型可生物降解的金纳米颗粒，在近红外区域具有等离子共振。纳米粒子将在体内降解为易于清除的成分，因此，将在金属纳米粒子用于癌症成像和治疗的巨大潜力与转化为临床实践之间提供一个重要的缺失环节。我们的合成方法基于将非常小的（小于 5 nm）初级金颗粒受控组装成总直径 <100 nm 和强近红外吸光度的纳米簇。该组装将由可生物降解的聚合物和初级纳米颗粒上的小帽配体介导。递送到体内后，纳米簇将随着时间的推移生物降解成亚6纳米配体封端的初级金纳米颗粒，这将非常有利于从体内快速清除。 这种聚合物/无机杂化材料将结合聚合物纳米颗粒的生物可降解性和金属纳米颗粒提供的强大成像对比度和治疗能力的优点。尽管这些纳米团簇将被证明在成像/治疗方面具有广泛的潜力，但我们将在这一特定应用中开发和优化可生物降解的等离激元纳米团簇，该纳米团簇具有强近红外吸光度，可用于癌细胞的光声成像（PA）。纳米簇将在口腔癌的生物学相关模型中进行评估。