Tian Chao, Qian Wei, Shao Xia, Xie Zhixing, Cheng Xu, Liu Shengchun, Cheng Qian, Liu Bing, Wang Xueding
Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USA.
IMRA America, Inc Ann Arbor MI 48105 USA.
Adv Sci (Weinh). 2016 Sep 7;3(12):1600237. doi: 10.1002/advs.201600237. eCollection 2016 Dec.
Detection and imaging of single cancer cells is critical for cancer diagnosis and understanding of cellular dynamics. Photoacoustic imaging (PAI) provides a potential tool for the study of cancer cell dynamics, but faces the challenge that most cancer cells lack sufficient endogenous contrast. Here, a type of colloidal gold nanoparticles (AuNPs) are physically fabricated and are precisely functionalized with quantitative amounts of functional ligands (i.e., polyethyleneglycol (PEG) and (Arginine(R)-Glycine(G)-Aspartic(D)) (RGD) peptides) to serve as an exogenous contrast agent for PAI of single cells. The functionalized AuNPs, with a fixed number of PEG but different RGD densities, are delivered into human prostate cancer cells. Radioactivity and photoacoustic analyses show that, although cellular uptake efficiency of the AuNPs linearly increases along with RGD density, photoacoustic signal generation efficiency does not and only maximize at a moderate RGD density. The functionalization of the AuNPs is in turn optimized based on the experimental finding, and single cancer cells are imaged using a custom photoacoustic microscopy with high-resolution. The quantitatively functionalized AuNPs together with the high-resolution PAI system provide a unique platform for the detection and imaging of single cancer cells, and may impact not only basic science but also clinical diagnostics on a range of cancers.
单个癌细胞的检测与成像对于癌症诊断和细胞动力学研究至关重要。光声成像（PAI）为癌细胞动力学研究提供了一种潜在工具，但面临着大多数癌细胞缺乏足够内源性对比度的挑战。在此，一种胶体金纳米颗粒（AuNPs）被物理制备，并精确地用定量的功能配体（即聚乙二醇（PEG）和（精氨酸（R）-甘氨酸（G）-天冬氨酸（D））（RGD）肽）进行功能化，以作为单细胞PAI的外源性造影剂。将具有固定数量PEG但不同RGD密度的功能化AuNPs递送至人前列腺癌细胞中。放射性和光声分析表明，尽管AuNPs的细胞摄取效率随RGD密度呈线性增加，但光声信号产生效率并非如此，仅在中等RGD密度时达到最大值。基于实验结果对AuNPs的功能化进行了优化，并用定制的高分辨率光声显微镜对单个癌细胞进行成像。定量功能化的AuNPs与高分辨率PAI系统一起为单个癌细胞的检测与成像提供了一个独特的平台，不仅可能影响基础科学，还可能影响一系列癌症的临床诊断。
