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

Kai Cheng, Sri Rajasekhar Kothapalli, Hongguang Liu, Ai Leen Koh, Jesse V. Jokerst, Han Jiang, Meng Yang, Jinbo Li, Jelena Levi, Joseph C. Wu, Sanjiv S. Gambhir, Zhen Cheng

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3560-3571
Number of pages12
JournalJournal of the American Chemical Society
Volume136
Issue number9
DOIs
StatePublished - Mar 5 2014

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Molecular imaging
Molecular Imaging
Photoacoustic effect
Gold
Imaging techniques
Tumors
Positron-Emission Tomography
Positron emission tomography
Peptides
Neoplasms
Bearings (structural)
Nanostructures
Subcutaneous Injections
Intravenous Administration
Nanoparticles
Toxicology
Contrast Media
Nanostructured materials
Toxicity
Animals

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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. / Construction and validation of nano gold tripods for molecular imaging of living subjects. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 9. pp. 3560-3571.
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Cheng, K, Kothapalli, SR, Liu, H, Koh, AL, Jokerst, JV, Jiang, H, Yang, M, Li, J, Levi, J, Wu, JC, Gambhir, SS & Cheng, Z 2014, 'Construction and validation of nano gold tripods for molecular imaging of living subjects', Journal of the American Chemical Society, vol. 136, no. 9, pp. 3560-3571. https://doi.org/10.1021/ja412001e

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

In: Journal of the American Chemical Society, Vol. 136, No. 9, 05.03.2014, p. 3560-3571.

Research output: Contribution to journalArticle

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AU - Cheng, Kai

AU - Kothapalli, Sri Rajasekhar

AU - Liu, Hongguang

AU - Koh, Ai Leen

AU - Jokerst, Jesse V.

AU - Jiang, Han

AU - Yang, Meng

AU - Li, Jinbo

AU - Levi, Jelena

AU - Wu, Joseph C.

AU - Gambhir, Sanjiv S.

AU - Cheng, Zhen

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N2 - 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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