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Molecular afterglow imaging with bright, biodegradable polymer nanoparticles

Nature Biotechnology volume 35, pages 1102–1110 (2017)Cite this article

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Abstract

Afterglow optical agents, which emit light long after cessation of excitation, hold promise for ultrasensitive in vivo imaging because they eliminate tissue autofluorescence. However, afterglow imaging has been limited by its reliance on inorganic nanoparticles with relatively low brightness and short-near-infrared (NIR) emission. Here we present semiconducting polymer nanoparticles (SPNs) <40 nm in diameter that store photon energy via chemical defects and emit long-NIR afterglow luminescence at 780 nm with a half-life of ∼6 min. In vivo, the afterglow intensity of SPNs is more than 100-fold brighter than that of inorganic afterglow agents, and the signal is detectable through the body of a live mouse. High-contrast lymph node and tumor imaging in living mice is demonstrated with a signal-to-background ratio up to 127-times higher than that obtained by NIR fluorescence imaging. Moreover, we developed an afterglow probe, activated only in the presence of biothiols, for early detection of drug-induced hepatotoxicity in living mice.

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Figure 1: Synthesis and characterization of SPNs.
Figure 2: Mechanistic study of the afterglow of SPNs.
Figure 3: 1O2-sensitizer-amplified NIR afterglow.
Figure 4: Tissue-penetration study of NIR afterglow luminescence.
Figure 5: In vivo afterglow imaging of lymph nodes and tumor.
Figure 6: Afterglow luminescence imaging of drug-induced hepatotoxicity.

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Acknowledgements

K.P. thanks Nanyang Technological University (Start-Up grant: NTUSUG: M4081627.120) and Singapore Ministry of Education (Academic Research Fund Tier 1 RG133/15 M4011559 and Tier 2 MOE2016-T2-1-098) for financial support. H.D. thanks Singapore Ministry of Education (Academic Research Fund Tier 2 MOE2015-T2-1-112 and Tier 3 MOE2013-T3-1-002) for financial support. J.V.J. thanks NIH HL 137187 and NIH HL 117048 grants for financial support.

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Authors and Affiliations

  1. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore

    Qingqing Miao, Chen Xie, Xu Zhen, Yan Lyu, Hongwei Duan & Kanyi Pu

  2. Department of Chemistry, National University of Singapore, Singapore

    Xiaogang Liu

  3. Department of NanoEngineering, University of California San Diego, La Jolla, California, USA

    Jesse V Jokerst

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Contributions

K.P. conceived and designed the study. Q.M. performed the nanoparticle synthesis and in vitro experiments. Q.M., C.X., X.Z. and Y. L. performed the in vivo experiments. K.P., Q.M., H.D., X. L. and J.V.J. contributed to the analysis and interpretation of results and preparation of the manuscript draft. K.P., Q.M., H.D., X.L., J.V.J. and all other authors contributed to the writing of this paper.

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Correspondence to Kanyi Pu.

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The authors declare no competing financial interests.

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Miao, Q., Xie, C., Zhen, X. et al. Molecular afterglow imaging with bright, biodegradable polymer nanoparticles. Nat Biotechnol 35, 1102–1110 (2017). https://doi.org/10.1038/nbt.3987

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