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Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice

Nature Nanotechnology volume 9, pages 233–239 (2014)Cite this article

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Abstract

Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species—vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes.

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Figure 1: Synthesis and characterization of SPNs.
Figure 2: Comparison of photoacoustic properties of SPN1 with SWNTs (1.2 × 150 nm) and GNRs (15 × 40 nm).
Figure 3: In vivo and ex vivo photoacoustic and fluorescent imaging of lymph nodes using SPN1.
Figure 4: In vitro characterization of RSPN for ROS sensing.
Figure 5: In vivo photoacoustic imaging of ROS generation from a mouse model of acute oedema using RSPN.

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Acknowledgements

The authors acknowledge the use of the SCi3 Core Facility. This work was supported by the National Institutes of Health (grants 2R01DK099800-06 and R21CA138353A2), the Stanford University National Cancer Institute (NCI) CCNE-T grant (U54CA151459) and In Vivo Cellular and Molecular Imaging Center (ICMIC) grant (P50CA114747). A.J.S. thanks the Susan G. Komen for the Cure for fellowship support. J.V.J. acknowledges a grant from NCI (5R25CA11868) and was supported by a postdoctoral fellowship (PF-13-098-01–CCE) from the American Cancer Society. J.M. and Z.B. acknowledge support from Air Force Office of Scientific Research for support of the synthesis of the polymers (FA9550-12-1-0190).

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  1. Kanyi Pu and Adam J. Shuhendler: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 1201 Welch Road, Stanford, 94305-5484, California, USA

    Kanyi Pu, Adam J. Shuhendler, Jesse V. Jokerst, Sanjiv S. Gambhir & Jianghong Rao

  2. Department of Chemical Engineering, Stanford University, Stanford, 94305-5025, California, USA

    Jianguo Mei & Zhenan Bao

  3. Department of Bioengineering and Department of Materials Science & Engineering, 318 Campus Drive, Stanford, 94305-5444, California, USA

    Sanjiv S. Gambhir

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Contributions

K.P., A.J.S. and J.R. conceived of the experiments. K.P. synthesized and characterized the nanoparticles. K.P. and A.J.S. performed in vitro and in vivo experiments. J.J. and S.S.G. provided GNRs, SWNTs and technical assistance with photoacoustic imaging. J.M. and Z.B. synthesized and provided SP2. K.P., A.J.S. and J.R. analysed the data and wrote the manuscript. All authors commented and contributed to the manuscript.

Corresponding author

Correspondence to Jianghong Rao.

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Competing interests

S.S.G. serves on the board of Endra and serves as a consultant for Visualsonics, both manufacturers of small animal photoacoustic imaging equipment.

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Pu, K., Shuhendler, A., Jokerst, J. et al. Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice. Nature Nanotech 9, 233–239 (2014). https://doi.org/10.1038/nnano.2013.302

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