Defining nanomaterial-biological interactions to enhance biocompatibility and bio

描述（由申请人提供）：纳米技术是一个有利的平台，由于纳米材料固有的独特物理和化学性质，它将为生物医学科学提供广泛的新应用和改进的技术。与有前途的生物医学纳米技术的发展和纳米材料的安全性有关的是对纳米材料-生物相互作用的透彻理解。然而，由于目前缺乏数据、纳米材料的巨大多样性以及缺乏共享发现和将数据转化为知识的协调努力，可能预测纳米材料与生物系统相互作用的主要特征尚未得到阐明。胚胎斑马鱼模型是一个动态的体内系统，提供了全动物研究的能力，方便细胞培养，快速评估工程纳米材料和生物系统之间的相互作用。使用该模型系统的调查可以揭示生物组织多个层面的微妙相互作用，即分子，细胞，系统，有机体。我们的方法将胚胎斑马鱼实验的许多优点与理想的纳米粒子平台结合起来，以便系统地评估各种理化参数对纳米材料暴露的整体生物反应的相对影响。在水环境中合成的高纯度、配体功能化的金纳米颗粒（AuNPs）可以精确地进行工程设计，从而可以独立评估材料的各个方面。众所周知，来自这一新兴领域的数据将是极其多样化的，包括大量正在/或将在广泛的动物系统和体外分析中进行测试的各种各样的纳米材料。纳米材料-生物相互作用的知识可能只有在纳入和考虑从该研究领域的全球努力中产生的整个数据体后才能得到。为了解决纳米生物技术新兴领域的这些需求，我们的团队开发了一个纳米材料-生物相互作用（NB）的协作知识库。NBI知识库是一个关于纳米材料表征、合成方法和纳米材料-生物相互作用在生物组织的多个层面上定义的注释数据的存储库。相关的计算、分析和数据挖掘工具将被纳入NBI框架，用于物种、路线、剂量和情景外推以及确定预测纳米材料生物相互作用所需的关键数据。公共卫生相关性：新的纳米材料正在迅速开发用于广泛的生物医学应用（例如，高性能诊断探针、位点选择治疗、假肢、再生医学、成像等），因此令人惊讶的是，人们对纳米材料如何或为什么与生物系统相互作用知之甚少，而对如何设计纳米材料以在整个动物中表现出预期效果的了解就更少了。迫切需要获得生物-纳米材料相互作用的全面信息，需要系统的、协作的科学研究来定义纳米材料-生物相互作用，并描述纳米材料的特定特性如何控制生物反应。及时评估和传播纳米材料-生物相互作用的信息将提供急需的数据，提高公众对纳米技术产业的信任，并为学术界和工业界的纳米材料设计者提供信息，以指导高性能、安全的纳米材料和由此产生的生物医学技术的发展。

DESCRIPTION (provided by applicant): Nanotechnology is an enabling platform that will provide a broad range of novel applications and improved technologies for biomedical science due to the unique physical and chemical properties inherent to nanomaterials. Pertinent to the development of promising biomedical nanotechnologies, and to the safety of nanomaterials in general, is a thorough understanding of nanomaterial-biological interactions. Yet, the principal characteristics that may be predictive of nanomaterial interactions with biological systems have not been elucidated because of the current lack of data, the enormous diversity of nanomaterials, and the lack of coordinated efforts to share findings and translate data into knowledge. The embryonic zebrafish model is a dynamic in vivo system that offers the power of whole-animal investigations with the convenience of cell culture to rapidly evaluate interactions between engineered nanomaterials and biological systems. Investigations using this model system can reveal subtle interactions at multiple levels of biological organization, i.e. molecular, cellular, systems, organismal. Our approach couples the many advantages of the embryonic zebrafish assay with an ideal nanoparticle platform in order to systematically assess the relative influence of various physiochemical parameters on overall biological responses to nanomaterial exposure. High-purity, ligand-functionalized gold nanoparticles (AuNPs) synthesized in aqueous environments can be precisely engineered such that individual aspects of the material can be evaluated independently. It is well understood that data from this emerging field will be extremely diverse including a multitude of widely varying nanomaterials that are being/or will be tested in a broad array of animal systems and in vitro assays. Knowledge of nanomaterial-biological interactions will likely only be arrived at upon inclusion and consideration of the entire body of data produced from global efforts in this research area. To address these needs in the nascent field of nanobiotechnology, our group has developed a collaborative knowledgebase of Nanomaterial-Biological Interactions (NB). The NBI knowledgebase serves as a repository for annotated data on nanomaterial characterization, synthesis methods, and nanomaterial-biological interactions define at multiple levels of biological organization. Relevant computational, analytic and data mining tools will be incorporated into NBI to the framework for species, route, dose and scenario extrapolations and for identification of key data required to predict the biological interactions of nanomaterials. PUBLIC HEALTH RELEVANCE: New nanomaterials are rapidly being developed for a wide range of biomedical applications (e.g. high-performance diagnostic probes, site-selective therapeutics, prosthetics, regenerative medicine, imaging, etc.), so it is surprising that so little is known about how or why nanomaterials interact with biological systems and even less is known about how to design them to exhibit a desired effect in whole animals. The immediate need to gain comprehensive information on biological-nanomaterial interactions requires systematic, collaborative scientific investigation to define nanomaterial-biological interactions and describe how specific properties of nanomaterials govern biological responses. Timely evaluation and dissemination of information on nanomaterial-biological interactions will provide much needed data, improve public trust of the nanotechnology industry, and provide nanomaterial designers in academia and industry with information to direct the development of high-performance, safe nanomaterials and resulting biomedical technologies.