Construction and validation of nano gold tripods for molecular imaging of living subjects.
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.
Molecular Imaging Program at Stanford (MIPS), ‡Canary Center at Stanford for Cancer Early Detection, §Department of Radiology and Bio-X Program, School of Medicine, ∥Stanford Nanocharacterization Laboratory, Stanford University , 1201 Welch Road, Lucas P095, Stanford, California 94305-5484, United States.
Kai
K
Cheng
Sri-Rajasekhar
SR
Kothapalli
Hongguang
H
Liu
Ai Leen
AL
Koh
Jesse V
JV
Jokerst
Han
H
Jiang
Meng
M
Yang
Jinbo
J
Li
Jelena
J
Levi
Joseph C
JC
Wu
Sanjiv S
SS
Gambhir
Zhen
Z
Cheng
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D049329:Nanostructures; D009842:Oligopeptides / Q000737:chemistry; D061088:Photoacoustic Techniques; D011092:Polyethylene Glycols / Q000737:chemistry; D049268:Positron-Emission Tomography
D009842:Oligopeptides; D011092:Polyethylene Glycols; D006046:Gold; C047981:arginyl-glycyl-aspartic acid