Construction and validation of nano gold tripods for molecular imaging of living subjects.

Construction and validation of nano gold tripods for molecular imaging of living subjects.
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纳米金三脚架的构建和验证,用于生存学科的分子成像。

DOI:
10.1021/ja412001e
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发表时间:
2014-03-05
影响因子:
15
通讯作者:
Cheng Z
Cheng Z
中科院分区:
化学1区
文献类型:
--
作者:
Cheng K;Kothapalli SR;Liu H;Koh AL;Jokerst JV;Jiang H;Yang M;Li J;Levi J;Wu JC;Gambhir SS;Cheng Z

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与具有规则结构的对应物相比,各向异性胶体混合纳米颗粒表现出优越的上级光学和物理性质。我们在此开发了一种受控的逐步策略,以构建具有预定组成和形态的新颖的、各向异性的、分支的金纳米结构(Au-三脚架)用于生物成像。所得的Au-三脚架的尺寸小于20 nm的显示出很大的希望,作为造影剂在体内光声成像(派)。我们进一步确定了金三脚架与两种可能的配置作为高吸收纳米材料从各种金多脚架使用数值模拟分析。皮下注射后,派信号与其浓度呈线性相关。使用小动物正电子发射断层扫描(PET)证实了有利于分子成像的金三足动物体内生物分布。静脉内施用环状Arg-Gly-Asp-d-Phe-Cys(RGDfC)肽缀合的Au-三足(RGD-Au-三足)至荷U87 MG肿瘤的小鼠显示出肿瘤中的派对比几乎比阻断组高3倍。派结果与相应的PET图像相关性良好。定量生物分布数据显示,在注射后24小时后,7.9%ID/g的RGD-Au-三脚架在U87 MG肿瘤中积累。一项初步小鼠毒理学研究证实,在组织病理学检查中未观察到显著急性或全身毒性的证据。我们的研究表明,金三脚架可以通过严格控制的化学合成可靠地合成,并可以作为新一代的平台,具有高选择性和灵敏度的多模态分子成像。
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.
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