申请者在仿生组织工程形成体外组织模型、多功能纳米金结构的构建及其在纳米医学的应用、纳米材料与细胞的相互作用等多方面取得了很多开创性的进展。本项目将充分利用美国Stevens Institute of Technology与厦门大学的科研条件进行合作研究，并结合纳米探针、谱学成像、微流控、肿瘤组织构建等关键技术，系统地开展以下几个方面的研究内容: （1）多功能纳米探针的构建；（2）多功能纳米探针的生物效应及机制；（3）多功能纳米探针用于细胞内实时、动态的生物分子检测。通过本项目的实施，我们将力争解决如下2个关键科学问题：（1）如何实现多功能纳米探针的集成设计优化；（2）如何实现细胞内生物分子（如ROS）高选择性、实时、动态、高灵敏及特异性的检测。本项目的实施将有力促进国际间合作与交流，并拓展我们在纳米生物医学领域的认识，促进我国纳米生物医学等领域的发展。

Closely monitoring the kinetics of intracellular biomolecules such as reactive oxygen species (ROS), especially in single cell, represents a promising avenue in order to mechanistically unfold the disease development, identify key markers for early diagnosis and develop targeted intervention for effective therapy. The design and fabrication of label-free, highly sensitive nanoprobes with versatile functionality is a key step toward intracellular monitoring. In consideration of the superior biocompatibility, noted optical properties, and versatile functionalization capacity, gold nanostructures are ideal candidates. With the established expertise in fabrication and modification of nanobiomaterials, modulation of nanomaterial/cell interactions and creation of microfluidics-based in vitro pathophysiologic tissue models as well as the common interest in utilizing gold nanostructures for cancer therapy and diagnosis, the applicants from Stevens Institute of Technology and Xiamen University are proposing a synergistic joint effort to primarily understand the spatiotemporal correlation between the dynamic progression of mitochondria and the cellular physiology. With the combination of innovative nanoprobes, spectral imaging, microfluidic cancer model, the proposed project will: 1) design and fabricate the multifunctional nanoprobes; 2) systematically evaluate the trafficking and biological functions of nanoprobes; and 3) utilize nanoprobes for realtime and dynamic detection of intracellular biomolecules. The joint efforts will not only promote the international collaboration and bilateral knowledge exchange, leverage the existing expertise of the applicants, but also significantly advance our knowledge base in nanomedicine and facilitate the progress on single cell detection. Upon successful execution of the proposed research, we expect to address at least two important scientific questions, including 1) how to integrate and optimize the multifunctional nanoprobes; and 2) how to real-time and dynamically detect intracellular biomolecules (e.g., ROS) with high selectivity, specificity and sensitivity.

本项目围绕着构建高灵敏度、多模态生物分子纳米探针这一核心问题，以纳米金颗粒为基础设计多种多模态纳米探针。包括了金纳米球/量子点（QDs）检测体系；金纳米棒（AuNR）自组装体荧光探针系统；AuNR-光敏剂诊疗一体化荧光探针，以及进一步拓展、优化了有应用价值的多模态纳米成像探针，构建了上转换纳米晶作为UCL/CT双模态生物成像探针。并在细胞水平和动物水平上进行了初步检测及成像应用。本项目的学术思维是: (1) 基于纳米金体系的金纳米棒（AuNR）/金纳米球荧光探针的制备及可控自组装的研究；(2) 将所制备的探针用于亚硝酸根离子、细胞内单线态氧产量、前列腺特异性抗原（PSA）的检测、生物成像和光热治疗；(3) 多功能上转换纳米成像探针的构建及其作为UCL/CT双模态生物探针在细胞水平和动物水平上的初步成像应用。在本项目中，我们采用多种成像、检测技术对所构建的纳米分子探针进行可行性分析，探索了多种探针在生物体内的初步成像效果。本项目为生物体组织及细胞内信号的检测分析提供了新思路，并探索了新方法。