Constructionand Validation of Nano Gold Tripods forMolecular Imaging of Living Subjects

摘要

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 revealedthat 7.9% ID/g of RGD-Au-tripods had accumulated in the U87MG tumorafter 24 h post-injection. A pilot mouse toxicology study confirmedthat no evidence of significant acute or systemic toxicity was observedin histopathological examination. Our study suggests that Au-tripodscan be reliably synthesized through stringently controlled chemicalsynthesis and could serve as a new generation of platform with highselectivity and sensitivity for multimodality molecular imaging.