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）：令人信服地表明，纳米技术可以提供独特的解决方案，以彻底改变许多破坏性疾病（例如癌症）的诊断和治疗。一个特别感兴趣的特定领域是开发用于分子特异性成像，治疗和组合成像/治疗的纳米颗粒。将无机纳米颗粒转换为全身靶向癌细胞的临床实践的主要障碍是它们的非生物降解性质。此外，用于生物应用中使用的涂层纳米颗粒的尺寸不足以轻松从体内清除。纳米颗粒的积累和由此产生的长期毒性是一个主要问题。在该研究计划中，我们将创建一类新的可生物降解金纳米颗粒，并在NIR地区具有等离子体共振。纳米颗粒将降低体内易于清除的成分，因此将在金属纳米颗粒在癌症成像和治疗中的巨大潜力以及转化为临床实践之间提供至关重要的缺失。我们的合成方法基于非常小的（小于5 nm）的基本金颗粒的受控组装成纳米群，其总直径<100 nm，并且具有强烈的NIR吸光度。该组件将由可生物降解的聚合物和一级纳米颗粒上的小盖配体介导。输送到体内后，纳米簇将随着时间的流逝而生物降解，以低于6 nm的配体限制的原代金纳米颗粒，这对于从体内的快速清除非常有利。 这种杂化聚合物/无机材料将结合聚合物纳米颗粒的生物降解性以及金属纳米颗粒提供的强大成像对比度和治疗能力的优势。尽管这些纳米簇在成像/治疗方面具有广泛的潜力，但我们将在这种特定的应用中开发和优化具有巨大NIR吸光度的可降解等离子纳米簇，以用于癌细胞的光声成像（PA）。纳米簇将在与口腔癌的生物学相关模型中进行评估。