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. ? ? ?
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