Defining nanomaterial-biological interactions to enhance biocompatibility and bio

描述(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特性，它将为生物医学科学提供广泛的新颖应用和改进的技术。与有前途的生物医学纳米技术的发展以及纳米材料的总体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，可能预测纳米材料与生物系统相互作用的主要特征尚未阐明，因为目前缺乏数据，纳米材料具有巨大的多样性，缺乏协调努力来分享研究结果并将数据转化为知识。斑马鱼胚胎模型是一个动态的活体系统，它提供了全动物研究的能力，并提供了细胞培养的便利，以快速评估工程纳米材料与生物系统之间的相互作用。使用这个模型系统的研究可以揭示生物组织的多个层面上的微妙相互作用，即分子、细胞、系统、有机体。我们的方法将斑马鱼胚胎试验的许多优点与理想的纳米颗粒平台结合起来，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)可以进行精确的工程设计，以便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，包括大量差异很大的纳米材料，这些材料正在/或将在广泛的动物系统和体外测试中进行测试。关于纳米材料-生物相互作用的知识可能只有在纳入和考虑这一研究领域的全球努力产生的整个数据之后才能实现。为了满足新兴纳米生物技术领域的这些需求，我们团队开发了一个关于纳米材料-生物相互作用(NB)的协作知识库。NBI知识库作为关于纳米材料表征、合成方法和纳米材料-生物相互作用注释数据的储存库，这些数据定义在生物组织的多个层次上。相关的计算、分析和数据挖掘工具将被纳入NBI，用于物种、路线、剂量和情景外推的框架，并用于确定预测纳米材料生物相互作用所需的关键数据。与公共健康相关：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，高性能诊断探头、部位选择疗法、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，更不知道如何设计它们，使其在整个动物身上显示出所需的效果。获取有关生物-纳米材料相互作用的全面信息的迫切需要需要系统、协作的科学调查，以界定纳米材料-生物相互作用，并描述纳米材料的特定性质如何支配生物反应。及时评估和传播有关纳米材料-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行业的信任，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.