State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecule Engineering of Hunan Province, Changsha 410082, People's Republic of China.
Acc Chem Res. 2013 Jul 16;46(7):1367-76. doi: 10.1021/ar3001525. Epub 2013 Mar 14.
Going in vivo, including living cells and the whole body, is very important for gaining a better understanding of the mystery of life and requires specialized imaging techniques. The diversity, composition, and temporal-spatial variation of life activities from cells to the whole body require the analysis techniques to be fast-response, noninvasive, highly sensitive, and stable, in situ and in real-time. Functionalized nanoparticle-based fluorescence imaging techniques have the potential to meet such needs through real-time and noninvasive visualization of biological events in vivo. Functionalized silica nanoparticles (SiNPs) doped with fluorescent dyes appear to be an ideal and flexible platform for developing fluorescence imaging techniques used in living cells and the whole body. We can select and incorporate different dyes inside the silica matrix either noncovalently or covalently. These form the functionalized hybrid SiNPs, which support multiplex labeling and ratiometric sensing in living systems. Since the silica matrix protects dyes from outside quenching and degrading factors, this enhances the photostability and biocompatibility of the SiNP-based probes. This makes them ideal for real-time and long-time tracking. One nanoparticle can encapsulate large numbers of dye molecules, which amplifies their optical signal and temporal-spatial resolution response. Integrating fluorescent dye-doped SiNPs with targeting ligands using various surface modification techniques can greatly improve selective recognition. Along with the endocytosis, functionalized SiNPs can be efficiently internalized into cells for noninvasive localization, assessment, and monitoring. These unique characteristics of functionalized SiNPs substantially support their applications in fluorescence imaging in vivo. In this Account, we summarize our efforts to develop functionalized dye-doped SiNPs for fluorescence imaging at the cell and small animal levels. We first discuss how to design and construct various functionalized dye-doped SiNPs. Then we describe their properties and imaging applications in cell surface receptor recognition, intracellular labeling, tracking, sensing, and controlled release. Additionally, we have demonstrated the promising application of dye-doped SiNPs as contrast imaging agents for in vivo fluorescence imaging in small animals. We expect these functionalized dye-doped SiNPs to open new opportunities for biological and medical research and applications.
在体（包括活细胞和整个生物体）研究对于更好地了解生命奥秘非常重要，需要专门的成像技术。从细胞到整个生物体的生命活动的多样性、组成和时空变化，要求分析技术具有快速响应、非侵入性、高灵敏度、稳定、原位和实时的特点。功能化纳米粒子基荧光成像技术有可能通过实时和非侵入性地可视化体内的生物事件来满足这些需求。荧光染料掺杂的功能化硅纳米粒子（SiNPs）似乎是开发用于活细胞和整个生物体的荧光成像技术的理想和灵活平台。我们可以选择并通过非共价或共价方式将不同的染料掺入到硅基质中。这些形成了功能化杂化 SiNPs，可以支持活系统中的多路标记和比率感应。由于硅基质可以保护染料免受外部猝灭和降解因素的影响，因此提高了基于 SiNP 探针的光稳定性和生物相容性。这使得它们非常适合实时和长时间跟踪。一个纳米粒子可以封装大量的染料分子，从而放大它们的光学信号和时空分辨率响应。通过各种表面修饰技术将荧光染料掺杂的 SiNPs 与靶向配体结合，可以大大提高选择性识别。随着内吞作用，功能化 SiNPs 可以有效地被内化到细胞中，用于非侵入性定位、评估和监测。这些独特的特性大大支持了功能化 SiNPs 在体内荧光成像中的应用。在本账目中，我们总结了我们为开发用于细胞和小动物水平荧光成像的功能化染料掺杂 SiNPs 所做的努力。我们首先讨论了如何设计和构建各种功能化染料掺杂 SiNPs。然后我们描述了它们在细胞表面受体识别、细胞内标记、跟踪、传感和控制释放方面的特性和成像应用。此外，我们已经证明了染料掺杂 SiNPs 作为小动物体内荧光成像对比造影剂的有前途的应用。我们期望这些功能化染料掺杂 SiNPs 为生物和医学研究和应用开辟新的机会。
