提出一种外泌体检测新方法，通过将表面增强拉曼散射（SERS）纳米探针固定在核酸适体（DNA）功能化水凝胶中，实现对肿瘤源性外泌体的高灵敏度光学检测。SERS纳米探针被用于识别肿瘤源性外泌体并产生指纹光学信号。SERS活性DNA功能化水凝胶（简称“SD水凝胶”）作为传感器，不仅提供了用于生物识别的三维反应位点，而且可放大SERS纳米探针的光学信号。选择性地与靶外泌体结合后，SERS纳米探针脱离SD水凝胶，导致SERS信号减弱，从而实现光学检测。通过SERS信号变化，SD水凝胶可以定量、灵敏地检测肿瘤源性外泌体，浓度检测限（LOD）约为22 μL^-1。该SD水凝胶将为临床癌症诊断提供一种新的技术手段。

As an emerging hybrid imaging modality, microwave-induced thermoacoustic imaging (MTAI), using microwaves as the excitation source and ultrasonic signals as the information carrier for combining the characteristics of high contrast of electromagnetic imaging and high resolution of ultrasound imaging, has shown broad prospects in biomedical and clinical applications. The imaging contrast depends on the microwave-absorption coefficient of the endogenous imaged tissue and the injected MTAI contrast agents. With systemically introduced functional nanoparticles, MTAI contrast and sensitivity can be further improved, and enables visualization of biological processes in vivo. In recent years, functional nanoparticles for MTAI have been developed to improve the performance and application range of MTAI in biomedical applications. This paper reviews the recent progress of functional nanoparticles for MTAI and their biomedical applications. The challenges and future directions of microwave thermoacoustic imaging with functional nanoparticles in the field of translational medicine are discussed.As an emerging hybrid imaging modality, microwave-induced thermoacoustic imaging (MTAI), using microwaves as the excitation source and ultrasonic signals as the information carrier for combining the characteristics of high contrast of electromagnetic imaging and high resolution of ultrasound imaging, has shown broad prospects in biomedical and clinical applications. The imaging contrast depends on the microwave-absorption coefficient of the endogenous imaged tissue and the injected MTAI contrast agents. With systemically introduced functional nanoparticles, MTAI contrast and sensitivity can be further improved, and enables visualization of biological processes in vivo. In recent years, functional nanoparticles for MTAI have been developed to improve the performance and application range of MTAI in biomedical applications. This paper reviews the recent progress of functional nanoparticles for MTAI and their biomedical applications. The challenges and future directions of microwave thermoacoustic imaging with functional nanoparticles in the field of translational medicine are discussed.

Functionalized black phosphorus (BP) nanosheets have been considered as promising nanoagents in cancer therapy due to their excellent photothermal conversion efficiency. However, it is still difficult to visually monitor the dynamic localization of BP nanoagents in cancer cells. In this paper, we systematically studied the second-harmonic generation (SHG) signals originating from exfoliated BP nanosheets. Interestingly, under the excitation of a high frequency pulsed laser at 950 nm, the SHG signals of BP nanosheets in vitro are almost undetectable because of their poor stability. However, the intracellular SHG signals from BP nanosheets could be measured by in vivo optical imaging due to the efficient enrichment of living HeLa cells. Moreover, the SHG signal intensity from BP nanosheets increases with the prolonged incubation time. It can be expected that the BP nanosheets could be a promising intracellular SHG nanoprobe employed for visually in vivo biomedical imaging in practical cancer photothermal therapy (PIT).

光热治疗基于光热药剂在激光照射下产生热量, 进而高温杀死肿瘤细胞, 因而实时监测光热过程中微观温度变化对于优化治疗效果具有十分重要的作用。稀土Eu3+配合物的发光具有线谱、长荧光寿命以及对温度高度敏感的特点, 利用Eu3+配合物的温敏特性可检测光热过程中的温度变化, 整合温度监测功能和光热特性的纳米体系在光热治疗领域具有很好的应用前景。本文制备了一种内部封装温度敏感探针Eu3+配合物且表面复合金纳米球的功能纳米颗粒, 将该功能纳米颗粒分散液置于不同的温度环境中, 发现其荧光性能对温度具有高的响应灵敏度, 即Eu3+的特征发射峰(615 nm)强度随温度升高降低52.7%, 表明该稀土荧光温度纳米传感器具有高的温度敏感性。在激光辐照下, 功能纳米颗粒可以产生良好的光热现象, 基于自身的温敏特性可实时对光热特性进行温度监控。

构建高转化效率的功能纳米探针是推动光声分子成像发展的关键。随着光声分子成像技术的发展, 具有非线性增强光声转换效率的自组装纳米探针逐渐成为研究热点, 然而有关其非线性增强的定量研究尚未见报道。本文以纳米金球为例, 利用有限元仿真定量探究金属纳米探针自组装诱导的非线性光热及光声效应, 揭示自组装纳米探针光声效应增强规律, 为构建具备高转换效率的光声自组装纳米探针奠定了理论基础。

为了实现光动力治疗过程中单线态氧的检测, 设计了一种水溶性良好的单线态氧纳米探针。首先利用再沉淀法将1,3二苯基异苯并呋喃(DPBF)封装于纳米颗粒中, 然后对纳米探针进行透射电镜、动态光散射粒径和吸收光谱表征, 表明纳米颗粒具有良好的分散性, 粒径约为200 nm, 在426 nm左右具有DPBF的特征吸收峰, 最后选择吲哚菁绿(ICG)作为光敏剂, 利用纳米探针的吸收峰变化检测单线态氧的产生。结果表明该纳米探针对单线态氧具有高灵敏度, 在光动力治疗过程中单线态氧的检测方面具有良好的应用价值。

提出一种新型的荧光及表面增强拉曼散射(SERS)双模式光学纳米探针。首先, 通过再沉淀-包覆法合成二氧化硅包覆香豆素6的纳米颗粒, 再在二氧化硅表面静电吸附多聚赖氨酸分子形成包覆层, 随后通过原位还原的方法在多聚赖氨酸壳层复合银纳米颗粒, 最后在银纳米颗粒表面吸附拉曼分子即形成双模式纳米探针。该探针通过二氧化硅包覆的荧光分子产生荧光信号, 以多聚赖氨酸表面的银纳米颗粒作为SERS增强基底, 利用拉曼分子获得SERS信号, 实现了荧光及SERS 双模式成像。荧光与表面增强拉曼散射相结合的双模式分析技术可同时发挥二者的优点, 提高成像的分辨率和灵敏度, 在生物医学领域具有重要的应用价值。

核酸是携带遗传信息的物质, 既存在于自然界中也能够通过成熟技术人工合成。通过体外筛选技术还可以筛选出具有特殊功能的核酸序列, 例如核酸适体和脱氧核酶。核酸通过沃森-克里克碱基互补配对原则进行杂交, 具有很强的专一性。无论是通过序列设计还是体外筛选, 核酸探针在生物标志物的分析与成像应用方面都发挥着重要作用。纳米材料辅助构建核酸功能化纳米探针, 可以保护负载的核酸探针不被核酸酶降解, 并且无需转染试剂就能进入细胞, 在细胞荧光成像应用上具有很大优势。为解决细胞内有些生物标志物含量低、难于检测的问题, 目前已构建多种适用于细胞水平的成像信号放大方法来实现对低丰度生物标志物的高灵敏成像。本文主要综述了核酸功能化纳米探针在细胞荧光成像中的应用进展, 包括反义寡核苷酸功能化纳米探针、核酸适体功能化纳米探针、脱氧核酶功能化纳米探针等, 同时介绍了他们在成像信号放大中的应用。

In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs) functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody to target the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aids their efficient immunospecific targeting through free Fab portions. The directional specificity of conjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophages treated with functionalized MNPs and free anti-HER2 antibody revealed that the antibody molecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe for molecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression.