Integrated Photothermal Nanoprobes

描述(由申请人提供)：关于细胞纳米级组件的大多数特征，包括这些组件的确切数量、位置、时间尺度、内部运动和相互作用，目前还存在知识空白。这种情况使得开发足够的、兼容的新的纳米设备或纳米结构材料用于细胞诊断和治疗变得困难。事实上，尽管在用作造影剂的各种纳米探针方面最近取得了进展，但它们在活细胞中的使用仍然存在一些限制。我们的目标是开发新型光热(PT)纳米探针，用于对处于自然状态的细胞进行快速(纳秒级)诊断和精确的细胞治疗。关键假设是，与抗体结合的PT纳米探针将直接在活细胞中自组装成纳米簇，这些纳米簇将具有协同特性，使它们对细胞新陈代谢期间空间组织的变化以及治疗干预非常敏感。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-治疗工具来实现。这种方法集成了纳米技术、成像技术、激光技术、显微技术和PT光谱学的进步，并有可能在生物医学方面有广泛的应用。我们将通过以下具体目标来追求这一目标：1.开发金纳米簇集成PT诊断和治疗的先进技术平台；2.探索纳米簇在体外活细胞中的诊断价值。这些研究的结果可能导致高灵敏度细胞诊断和增强热疗的新概念，使用纳米颗粒可以在活细胞中自组装成新的、所需的纳米结构(例如纳米簇)，其协同特性可以通过激光能量激活。由于PT诊断和选择性光热分解基于相似的热效应，它们集成到一个多功能系统中可以为癌症的治疗提供反馈，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用于医疗应用的新型簇状纳米材料的所需特性提出建议。

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.