Integrated Photothermal Nanoprobes

描述（由申请人提供）：关于细胞纳米级组分的大多数特征，包括这些组分的确切数量、它们的位置、时间尺度、内部运动和相互作用，存在知识空白。这种状况使得难以开发用于细胞诊断和治疗的足够的、兼容的新纳米器件或纳米结构材料。事实上，尽管最近在用作造影剂的各种纳米探针方面取得了进展，但它们在活细胞中的使用仍然具有一些限制。我们的目标是开发新型光热（PT）纳米探针，用于快速（纳秒级）诊断天然状态下的细胞和精确的细胞治疗。关键假设是，与抗体缀合的PT纳米探针将直接在活细胞中自组装成纳米簇，并且这些纳米簇将具有协同特性，使得它们对细胞代谢期间的空间组织变化以及治疗干预极其敏感。协同效应的快速激光激活及其同时评估可以通过集成的PT诊断-治疗工具实现。这种方法集成了纳米技术，成像，激光技术，显微镜和PT光谱学的进步，并可能具有广泛的生物医学应用。我们将通过以下具体目标来实现这一目标：1.利用金纳米团簇开发PT诊断和治疗的先进技术平台; 2.探讨纳米团簇在体外活细胞中的诊断价值。这些研究的结果可能会带来高灵敏度细胞诊断和使用纳米颗粒增强热疗法的新概念，这些纳米颗粒可以在活细胞中自组装成新的、所需的纳米结构（例如，纳米团簇），其协同性质可以用激光能量激活。由于PT诊断和选择性光热疗法基于相似的热效应，因此将其集成到多功能系统中可以为癌症治疗提供反馈，以优化和实时评估治疗效果。这些研究的结果还将使人们有可能就新的、成簇的纳米材料在医疗应用中的理想特性提出建议。

DESCRIPTION (provided by applicant): Gaps in knowledge exist about most of the characteristics of the nanoscale components of cells, including the exact quantities of such components, their locations, time scales, internal motions, and interactions. This state of affairs makes it difficult to develop adequate, compatible new nanodevices or nanostructure materials for cellular diagnostics and therapeutics. Indeed, despite recent advances in various nanoprobes used as contrast agents, their use in living cells still has some limitations. Our goal is to develop new types of photothermal (PT) nanoprobes for both rapid (nanosecond scale) diagnostics of cells in their native state and precise cellular therapy. Key hypotheses are that PT nanoprobes conjugated with antibodies will self- assemble into nanoclusters directly in living cells and that these nanoclusters will have synergistic properties that make them extremely sensitive to changes in spatial organization during cell metabolism, as well as therapeutic interventions. The rapid laser activation of synergistic effects, with their simultaneous assessment, can be realized with an integrated PT diagnostic-therapeutic tool. This approach integrates advances in nanotechnology, imaging, laser techniques, microscopy, and PT spectroscopy and potentially will have a broad-spectrum of biomedical applications. We will pursue this goal through the following Specific Aims: 1. Develop the advanced technical platform for integrated PT diagnostics and therapeutics with gold nanoclusters, and 2. Explore the diagnostic value of nanoclusters in living cells in vitro. The results of these studies may lead to new concepts of high-sensitivity cell diagnostics and enhanced thermal therapy with the use of nanoparticles that can self-assemble in living cells into new, desired nanostructures (e.g., nanoclusters) whose synergistic properties can be activated with laser energy. Because PT diagnostics and selective photothermolysis are based on similar thermal effects, their integration into a multifunctional system may provide treatment of cancer with feedback for optimization and real-time assessment of therapeutic efficacy. The results of these studies will also make it possible to formulate recommendations on the desired properties of new, clustered nanomaterials for medical applications.