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In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles

Nature Materials volume 6, pages 765–769 (2007)Cite this article

Abstract

The overproduction of hydrogen peroxide is implicated in the development of numerous diseases1,2,3,4 and there is currently great interest in developing contrast agents that can image hydrogen peroxide in vivo. In this report, we demonstrate that nanoparticles formulated from peroxalate esters and fluorescent dyes can image hydrogen peroxide in vivo with high specificity and sensitivity. The peroxalate nanoparticles image hydrogen peroxide by undergoing a three-component chemiluminescent reaction between hydrogen peroxide, peroxalate esters and fluorescent dyes. The peroxalate nanoparticles have several attractive properties for in vivo imaging, such as tunable wavelength emission (460–630 nm), nanomolar sensitivity for hydrogen peroxide and excellent specificity for hydrogen peroxide over other reactive oxygen species. The peroxalate nanoparticles were capable of imaging hydrogen peroxide in the peritoneal cavity of mice during a lipopolysaccharide-induced inflammatory response. We anticipate numerous applications of peroxalate nanoparticles for in vivo imaging of hydrogen peroxide, given their high specificity and sensitivity and deep-tissue-imaging capability.

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Figure 1: Peroxalate nanoparticles—a new strategy for imaging hydrogen peroxide in vivo.
Figure 2: Peroxalate nanoparticles have high sensitivity and specificity for hydrogen peroxide, and also tunable emission wavelengths.
Figure 3: In vivo imaging of exogenous hydrogen peroxide using peroxalate nanoparticles.
Figure 4: In vivo imaging of endogenous hydrogen peroxide in the peritoneal cavity of mice, during an LPS-induced inflammatory response, using peroxalate nanoparticles.

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Acknowledgements

This work was supported by the Georgia Tech/Emory Center for the Engineering of Living Tissues (funded by NSF-EEC-9731643) (N.M.), NSF-BES-0546962 Career Award (N.M.), NIH UO1 HL80711-01 (N.M.), NIH R21 EB006418 (N.M.), J&J/GT Health Care Innovation Seed Grant Proposal (N.M.) and NIH P01 HL58000 (W.R.T.). The authors would like to thank R. Dasari (Department of Chemistry, Georgia Institute of Technology) for nuclear magnetic resonance and Fourier transform infrared analysis.

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Author notes

  1. Dongwon Lee and Sirajud Khaja: These authors contributed equally to this work

Authors and Affiliations

  1. The Wallace H. Coulter Department of Biomedical Engineering and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA

    Dongwon Lee, Sirajud Khaja, Madhuri Dasari, W. Robert Taylor & Niren Murthy

  2. Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA

    Juan C. Velasquez-Castano & W. Robert Taylor

  3. Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA

    Carrie Sun & John Petros

  4. The Atlanta VA Medical Center, Decatur, Georgia 30033, USA

    John Petros & W. Robert Taylor

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  1. Dongwon Lee
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Correspondence to Niren Murthy.

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Lee, D., Khaja, S., Velasquez-Castano, J. et al. In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles. Nature Mater 6, 765–769 (2007). https://doi.org/10.1038/nmat1983

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