热活化延迟荧光材料敏化的高效率红光磷光纳米粒子的设计、合成及其时间分辨成像应用

Time-resolved technology can effectively remove the interference of background fluorescence and various scattered light, and significantly increase the signal-to-noise ratio，which has important applications in bioimaging. But there are a few of bioprobes with a long luminescence lifetime of µs or above. In recent years, a variety of luminescent materials with long lifetime, such as metal complexes, room-temperature phosphor molecules, and thermally activated delayed fluorescence (TADF) compounds, have been prepared into nanoparticles and used as time-resolved probes. However, these nanomaterials have low emitting efficiency in red part of spectrum and lack of methods for targeted detection, which are far from meeting the various requirements of time-resolved bioimaging. In the project, an energy transfer system of receptor and donor was constructed in nanoparticles by homogeneous doping, in which thermally activated delayed fluorescence (TADF) conjugated polymer was used as the donor and red phosphor metal complex was used as the receptor. Thus high-brightness red long-life nanomaterials will be prepared and applied to cell and mouse imaging. On this basis, amphiphilic polymers that are sensitive to pH, reactive oxygen species (ROS) or enzyme are selected to prepare smart nanomaterials for targeted imaging. This project aims to promote the further application of time-resolved technology in the biological field based on long-lived luminescent materials.

时间分辨技术可以有效去除背景荧光以及各种散射光的干扰，显著提高检测信噪比，在生物成像领域有重要应用。然而发光寿命长在µs级别及以上的生物探针较少。近年来金属配合物、室温磷光分子、延迟荧光（TADF）化合物等各种长寿命材料被制备成纳米粒子用作时间分辨探针。但这些纳米粒子的红光发光效率低，同时缺少靶向成像方法，远不能满足各种不同的时间分辨成像需求。本项目拟以热活化延迟荧光（TADF）共轭聚合物为给体，红光磷光金属配合物为受体，在纳米粒子内构建给体、受体均相掺杂的能量转移体系，制备高亮度红光长寿命纳米材料，并进行细胞及小鼠成像。在此基础上选用对pH、活性氧（ROS）敏感或酶响应的两亲性聚合物，制备具有应激响应性的智能纳米材料以实现靶向成像。本项目旨在推进基于长寿命发光材料的时间分辨技术在生物领域的进一步应用。

时间分辨技术可以有效去除背景荧光以及各种散射光的干扰，显著提高检测信噪比，在生物成像领域有重要应用。然而发光寿命在μs级别及以上的生物探针较少，且近年来基于过渡态金属配合物、有机室温磷光化合物、热活化延迟荧光（TADF）化合物等长寿命材料水溶性较差，所制成的纳米粒子的红光发光效率也很低，远不能满足各种不同的时间分辨成像的需求。本项目选用TADF共轭聚合物为给体，红光磷光金属配合物为受体，成功构建了给体、受体均相掺杂的能量转移体系，制备了红光磷光纳米粒子。实验结果表明，由TADF聚合物和Ir配合物组成能量转移体系最高能将量子产率提升至50 %，纳米粒子在水和活细胞中均能观察到很明显的橙红色发光。在此基础上，进一步通过在纳米粒子上非共价修饰细胞穿膜肽（CPPs），成功地促进了纳米粒子在细胞内的富集，更有利于活细胞的时间分辨发光成像。最后，本项目研究了小分子给体敏化受体的纳米体系，因具有更长的发光寿命可用于自搭建仪器上的时间分辨成像。本项目构建了一种通用简单的长寿命发光增强纳米体系，进一步推进了基于长寿命发光材料的时间分辨技术在生物领域的应用。