Vonnemann Jonathan, Beziere Nicolas, Böttcher Christoph, Riese Sebastian B, Kuehne Christian, Dernedde Jens, Licha Kai, von Schacky Claudio, Kosanke Yvonne, Kimm Melanie, Meier Reinhard, Ntziachristos Vasilis, Haag Rainer
1. Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany;
2. Chair for Biological Imaging, Technische Universität München, 81675 Munich, Germany and Institute for Biological and Medical Imaging, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
Theranostics. 2014 Mar 20;4(6):629-41. doi: 10.7150/thno.8518. eCollection 2014.
We have synthesized a targeted imaging agent for rheumatoid arthritis based on polysulfated gold nanorods. The CTAB layer on gold nanorods was first replaced with PEG-thiol and then with dendritic polyglycerolsulfate at elevated temperature, which resulted in significantly reduced cytotoxicity compared to polyanionic gold nanorods functionalized by non-covalent approaches. In addition to classical characterization methods, we have established a facile UV-VIS based BaCl2 agglomeration assay to confirm a quantitative removal of unbound ligand. With the help of a competitive surface plasmon resonance-based L-selectin binding assay and a leukocyte adhesion-based flow cell assay, we have demonstrated the high inflammation targeting potential of the synthesized gold nanorods in vitro. In combination with the surface plasmon resonance band of AuNRs at 780 nm, these findings permitted the imaging of inflammation in an in vivo mouse model for rheumatoid arthritis with high contrast using multispectral optoacoustic tomography. The study offers a robust method for otherwise difficult to obtain covalently functionalized polyanionic gold nanorods, which are suitable for biological applications as well as a low-cost, actively targeted, and high contrast imaging agent for the diagnosis of rheumatoid arthritis. This paves the way for further research in other inflammation associated pathologies, in particular, when photothermal therapy can be applied.
我们基于多硫酸化金纳米棒合成了一种用于类风湿性关节炎的靶向成像剂。金纳米棒上的十六烷基三甲基溴化铵层首先被聚乙二醇硫醇取代，然后在高温下被树枝状聚甘油硫酸酯取代，与通过非共价方法功能化的聚阴离子金纳米棒相比，其细胞毒性显著降低。除了经典的表征方法外，我们还建立了一种基于紫外可见光谱的简便氯化钡团聚测定法，以确认未结合配体的定量去除。借助基于表面等离子体共振的竞争性L-选择素结合测定法和基于白细胞粘附的流动池测定法，我们在体外证明了合成的金纳米棒具有高炎症靶向潜力。结合金纳米棒在780nm处的表面等离子体共振带，这些发现使得利用多光谱光声断层扫描在类风湿性关节炎体内小鼠模型中以高对比度对炎症进行成像成为可能。该研究提供了一种强有力的方法来制备原本难以获得的共价功能化聚阴离子金纳米棒，其适用于生物应用，也是一种用于类风湿性关节炎诊断的低成本、主动靶向且高对比度的成像剂。这为其他炎症相关病理学的进一步研究铺平了道路，特别是在可以应用光热疗法的情况下。
