Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 136, Issue 9, Pages 3560-3571Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja412001e
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Funding
- Office of Science (BER)
- U.S. Department of Energy [DE-SC0008397]
- NIH In vivo Cellular Molecular Imaging Center (ICMIC) [1350 CA114747]
- NIH [5R01 HL093172]
- NCI Cancer Center Nanotechnology Excellence Grant (CCNE-TR) [U54 CA119367, CA151459]
- U.S. Department of Energy (DOE) [DE-SC0008397] Funding Source: U.S. Department of Energy (DOE)
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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 (PAT). We further identified Au-tripods with two possible configurations as high-absorbance nanomaterials from various gold multipods using a numerical simulation analysis. The PAT 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 PAL contrasts in tumors almost 3-fold higher than for the blocking group. PAT 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.
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