Construction and Validation of Nano Gold Tripods for Molecular Imaging of Living Subjects

• Published in: Journal of the American Chemical Society Vol. 136; no. 9; pp. 3560 - 3571
• Main Authors: Cheng, Kai, Kothapalli, Sri-Rajasekhar, Liu, Hongguang, Koh, Ai Leen, Jokerst, Jesse V, Jiang, Han, Yang, Meng, Li, Jinbo, Levi, Jelena, Wu, Joseph C, Gambhir, Sanjiv S, Cheng, Zhen
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05.03.2014
• Subjects: Animals; Cell Line, Tumor; Female; gold; Gold - chemistry; Gold - pharmacokinetics; histopathology; Humans; image analysis; intravenous injection; mathematical models; Mice; Molecular Imaging - methods; nanoparticles; Nanostructures; neoplasms; Oligopeptides - chemistry; Photoacoustic Techniques; physical properties; Polyethylene Glycols - chemistry; Positron-Emission Tomography; subcutaneous injection; synthesis; toxicity; toxicology
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja412001e

Anisotropic colloidal hybrid nanoparticles exhibit superior optical and physical properties compared to their counterparts with regular architectures. We herein developed a controlled, stepwise strategy to build novel, anisotropic, branched, gold nanoarchitectures (Au-tripods) with predetermined composition and morphology for bioimaging. The resultant Au-tripods with size less than 20 nm showed great promise as contrast agents for in vivo photoacoustic imaging (PAI). We further identified Au-tripods with two possible configurations as high-absorbance nanomaterials from various gold multipods using a numerical simulation analysis. The PAI signals were linearly correlated with their concentrations after subcutaneous injection. The in vivo biodistribution of Au-tripods favorable for molecular imaging was confirmed using small animal positron emission tomography (PET). Intravenous administration of cyclic Arg-Gly-Asp-d-Phe-Cys (RGDfC) peptide conjugated Au-tripods (RGD-Au-tripods) to U87MG tumor-bearing mice showed PAI contrasts in tumors almost 3-fold higher than for the blocking group. PAI results correlated well with the corresponding PET images. Quantitative biodistribution data revealed that 7.9% ID/g of RGD-Au-tripods had accumulated in the U87MG tumor after 24 h post-injection. A pilot mouse toxicology study confirmed that no evidence of significant acute or systemic toxicity was observed in histopathological examination. Our study suggests that Au-tripods can be reliably synthesized through stringently controlled chemical synthesis and could serve as a new generation of platform with high selectivity and sensitivity for multimodality molecular imaging.