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Nanoparticles with ultrasound-induced afterglow luminescence for tumour-specific theranostics

Nature Biomedical Engineering volume 7, pages 298–312 (2023)Cite this article

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Abstract

Molecular imaging via afterglow luminescence minimizes tissue autofluorescence and increases the signal-to-noise ratio. However, the induction of afterglow requires the prior irradiation of light, which is attenuated by scattering and absorption in tissue. Here we report the development of organic nanoparticles producing ultrasound-induced afterglow, and their proof-of-concept application in cancer immunotheranostics. The ‘sonoafterglow’ nanoparticles comprise a sonosensitizer acting as an initiator to produce singlet oxygen and subsequently activate a substrate for the emission of afterglow luminescence, which is brighter and detectable at larger tissue depths (4 cm) than previously reported light-induced afterglow. We formulated sonoafterglow nanoparticles containing a singlet-oxygen-cleavable prodrug for the immune-response modifier imiquimod that specifically turn on in the presence of the inflammation biomarker peroxynitrite, which is overproduced by tumour-associated M1-like macrophages. Systemic delivery of the nanoparticles allowed for sonoafterglow-guided treatment of mice bearing subcutaneous breast cancer tumours. The high sensitivity and depth of molecular sonoafterglow imaging may offer advantages for the real-time in vivo monitoring of physiopathological processes.

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Fig. 1: Screening and optimization of SNAPs.
Fig. 2: Deep-tissue induction of sonoafterglow.
Fig. 3: Activatable sonoafterglow imaging of M1 macrophages.
Fig. 4: Sonoafterglow cancer immunotheranostics in vitro.
Fig. 5: In vivo sonoafterglow cancer theranostics.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analyzed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding author on reasonable request. Source data are provided with this paper.

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Acknowledgements

K.P. acknowledges financial support from the Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005), and the Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20) and Academic Research Fund Tier 2 (MOE-T2EP30220-0010).

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Author notes

  1. These authors contributed equally: Cheng Xu, Jingsheng Huang.

Authors and Affiliations

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

    Cheng Xu, Jingsheng Huang, Yuyan Jiang, Shasha He, Chi Zhang & Kanyi Pu

  2. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Kanyi Pu

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Contributions

K.P. conceived and designed the study. C.X. and Y.J. performed nanoparticle construction. C.X. performed in vivo experiments. J.H. performed the chemical synthesis. C.X., S.H. and C.Z. performed in vitro characterization and cell experiments. K.P. and C.X. analyzed the data and drafted the manuscript. All authors contributed to the writing of the manuscript.

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Correspondence to Kanyi Pu.

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Xu, C., Huang, J., Jiang, Y. et al. Nanoparticles with ultrasound-induced afterglow luminescence for tumour-specific theranostics. Nat. Biomed. Eng 7, 298–312 (2023). https://doi.org/10.1038/s41551-022-00978-z

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