Institute of Biomaterials and Biomedical Engineering, University of Toronto , Rosebrugh Building, Room 407, 164 College Street, Toronto, Ontario M5S 3G9, Canada.
Department of Immunology, University of Toronto , Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
J Am Chem Soc. 2017 Jul 26;139(29):9961-9971. doi: 10.1021/jacs.7b04022. Epub 2017 Jul 13.
Chemical probes are key components of the bioimaging toolbox, as they label biomolecules in cells and tissues. The new challenge in bioimaging is to design chemical probes for three-dimensional (3D) tissue imaging. In this work, we discovered that light scattering of metal nanoparticles can provide 3D imaging contrast in intact and transparent tissues. The nanoparticles can act as a template for the chemical growth of a metal layer to further enhance the scattering signal. The use of chemically grown nanoparticles in whole tissues can amplify the scattering to produce a 1.4 million-fold greater photon yield than obtained using common fluorophores. These probes are non-photobleaching and can be used alongside fluorophores without interference. We demonstrated three distinct biomedical applications: (a) molecular imaging of blood vessels, (b) tracking of nanodrug carriers in tumors, and (c) mapping of lesions and immune cells in a multiple sclerosis mouse model. Our strategy establishes a distinct yet complementary set of imaging probes for understanding disease mechanisms in three dimensions.
化学探针是生物成像工具箱的关键组成部分，因为它们可以标记细胞和组织中的生物分子。生物成像的新挑战是设计用于三维（3D）组织成像的化学探针。在这项工作中，我们发现金属纳米粒子的光散射可以为完整和透明的组织提供 3D 成像对比度。纳米粒子可以作为金属层化学生长的模板，进一步增强散射信号。在整个组织中使用化学生长的纳米粒子可以放大散射，产生比使用常见荧光团获得的光子产率高 140 万倍。这些探针不会发生光漂白，可以与荧光团一起使用而不会产生干扰。我们展示了三个不同的生物医学应用：（a）血管的分子成像，（b）肿瘤中纳米药物载体的跟踪，以及（c）多发性硬化症小鼠模型中病变和免疫细胞的映射。我们的策略为理解三维疾病机制建立了一组独特但互补的成像探针。
