Biodegradable Plasmonic Nanoparticles for Cancer Imaging and Therapy

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，以彻底改变许多毁灭性疾病（如癌症）的诊断和治疗。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。将无机纳米颗粒转化为用于癌细胞的全身靶向的临床实践的主要障碍是其不可生物降解的性质。此外，在生物应用中使用的包覆纳米颗粒的尺寸不够小，不能容易地从体内清除。纳米颗粒的累积和由此产生的长期毒性是一个主要问题。在这项研究计划中，我们将创建一类新的可生物降解的金纳米粒子与等离子体共振在近红外区域。纳米颗粒将降解为体内易于清除的成分，因此，将在金属纳米颗粒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关键的缺失环节。我们的合成方法是基于非常小（小于5 nm）的初级金颗粒的控制组装成纳米团簇，具有<100 nm的总直径和强烈的近红外吸收。组装将由可生物降解的聚合物和初级纳米颗粒上的小封端配体介导。在递送到体内后，纳米团簇将随时间生物降解成亚6 nm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和金属纳米颗粒提供的强成像对比度和治疗能力的联合收割机优点。鉴于这些纳米团簇将被证明在成像/治疗中具有广泛的潜力，我们将在此特定应用中开发和优化具有强NIR吸收的可生物降解等离子体纳米团簇，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。 公共卫生相关性：纳米技术可以提供独特的解决方案，彻底改变许多毁灭性疾病（如癌症）的诊断和治疗。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。将无机纳米颗粒转化为全身靶向癌细胞的临床实践的一个主要障碍是它们在体内的积累并导致长期毒性。在这项研究计划中，我们将创建一类新的可生物降解的金纳米粒子与等离子体共振在近红外区域。纳米颗粒将降解为体内易于清除的成分，因此，将在金属纳米颗粒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关键的缺失环节。

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. PUBLIC HEALTH RELEVANCE: 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 accumulation in the body and resulting long-term toxicity. 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.