DNA-carbon Assemblies for Multispectral Imaging

描述（由申请人提供）：本研究旨在使用DNA骨架构建石墨烯和石墨的分子定义的烃片段，以形成高荧光组装体。这些DNA-碳组装体具有半导体量子点的许多有用的电子物理特性。然而，它们为这些量子点的许多局限性提供了解决方案：它们在结构上是均匀的，易于合成并易于与生物分子缀合，是细胞可渗透的，并且几乎没有毒性。这项工作在几个方面是新颖的：它提供了一种新的方法来组装具有完整结构控制的层状碳氢化合物（石墨烯）片;它提供了这些不寻常的量子发光组件的新型生物缀合物;它提供了新的标签，使多个细胞抗原同时成像。 我们的初步工作表明，这样的DNA-碳组件（CA）是多光谱标记，是细胞可渗透的，可以很容易地结合到抗体和其他感兴趣的蛋白质。然而，要开发这些DNA-CA用于生物医学应用，还需要做更多的工作。我们的具体研究计划是系统地改变CA的大小和几何形状，以更好地了解结构如何影响其基本的物理性质。利用这些知识，我们将构建CA发射在广泛的波长范围内的多光谱成像的实际应用，我们将开发新的策略，他们的生物共轭，然后我们将通过两种方法将它们应用于成像生物学和临床相关抗原。 这项研究对基础生物医学和应用生物医学都有重要意义。我们的方法提供了对纳米级层状碳组件的完整结构控制，通过产生可重复且易于生产的结构来解决该领域的主要问题。我们的结构设计保留了量子点的有用的生物物理性质，同时解决了它们在生物应用中的许多主要限制：难以缀合、多价、溶解性差、毒性、细胞渗透性差。我们期望从这项工作中获得近期有用的结果，包括可以广泛应用于生物成像的标记，以及用于诊断B细胞淋巴瘤的多抗原成像的改进方法的演示。

DESCRIPTION (provided by applicant): This research is aimed at the use of the DNA backbone to construct molecularly defined hydrocarbon fragments of graphene and graphite to form highly fluorescent assemblies. These DNA-carbon assemblies possess many of the useful photophysical characteristics of semiconductor quantum dots. However, they offer solutions to many of the limitations of those quantum dots: they are structurally homogeneous, are easily synthesized and readily conjugated to biomolecules, are cell permeable, and have little or no toxicity. This work is novel in several ways: it offers a new way to assemble layered hydrocabon (graphene) sheets with complete structural control; it offers novel bioconjugates of these unusual quantum luminescent assemblies; and it provides new labels that enable the imaging of multiple cellular antigens simultaneously. Our preliminary work has shown that such DNA-carbon assemblies (CAs) are multispectral labels that are cell-permeable and can be easily conjugated to antibodies and other proteins of interest. To develop these DNA-CAs for biomedical applications, however, more work is needed. Our specific research plans are to vary CA size and geometry systematically to gain an improved understanding of how structure influences their basic photophysical properties. Using this knowledge, we will construct CAs emitting in a wide range of wavelengths for practical applications in multispectral imaging; we will develop new strategies for their bioconjugation; and we will then apply them in imaging biologically and clinically relevant antigens by two approaches. This research will be important both to basic biomedical science and to applied biomedicine. Our approach offers complete structural control over nanometer-scale layered carbon assemblies, solving a major problem in the field by yielding repeatable and easily produced structures. Our structural design retains the useful photophysical properties of quantum dots, while addressing many of their major limitations in biological applications: difficult conjugation, polyvalency, poor solubility, toxiciy, poor cell permeability. We expect near-term useful results from this work, including labels that can be broadly applied in biological imaging, and demonstration of improved methods for multiantigen imaging in diagnosis of B-cell lymphomas.