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Physical activation of innate immunity by spiky particles

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Abstract

Microbial biochemicals have been indicated as the primary stimulators of innate immunity, the first line of the body’s defence against infections. However, the influence of topological features on a microbe’s surface on immune responses remains largely unknown. Here we demonstrate the ability of TiO2 microparticles decorated with nanospikes (spiky particles) to activate and amplify the immune response in vitro and in vivo. The nanospikes exert mechanical stress on the cells, which results in potassium efflux and inflammasome activation in macrophages and dendritic cells during phagocytosis. The spiky particles augment antigen-specific humoral and cellular immune responses in the presence of monophosphoryl lipid A and elicit protective immunity against tumour growth and influenza viral infection. The study offers insights into how surface physical cues can tune the activation of innate immunity and provides a basis for engineering particles with increased immunogenicity and adjuvanticity.

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Fig. 1: Schematic and particle fabrication.
Fig. 2: BMM viability and cell–particle interface study.
Fig. 3: BMM–particle interface study via confocal fluorescence microscopy.
Fig. 4: Spiky particles activate inflammasomes.
Fig. 5: Spiky particles enhance DC maturation and DC-meditated cancer immunotherapy.
Fig. 6: Spiky particles coupled with MPL as a potent adjuvant.

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Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work is supported in part by the National Natural Science Foundation of China (grant nos 61771498, 51705543 and 31530023) to X.X., J.T. and T.H., and by National Institutes of Health grants AI089779 and AI 113458 and department funds to M.X.W. X.X. thanks the Youth 1000 Talents Program of China and 100 Talents Program of Sun Yat-Sen University (76120-18821104). J.W. thanks the 100 Talents Program of Sun Yat-Sen University. The authors thank the Wellman Center Photopathology Core for their help in the histology analysis during this project.

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  1. These authors contributed equally: Ji Wang, Hui-Jiuan Chen.

Authors and Affiliations

  1. State Key Laboratory of Optoelectronic Materials and Technologies, School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, China

    Ji Wang, Hui-Jiuan Chen, Tian Hang, Guishi Liu, Gen He, Shuai Xiao, Bo-ru Yang, Chengduan Yang, Fanmao Liu, Jun Tao & Xi Xie

  2. Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA, USA

    Ji Wang, Yang Yu, Guishi Liu & Mei X. Wu

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Contributions

J.W., H.-J.C., T.H., G.L., G.H., B.Y., J.T., M.X.W. and X.X. designed experiments, analysed data and wrote the manuscript. J.W., H.-J.C., T.H., Y.Y., G.L., G.H., S.X., C.Y. and X.X. performed the experiments. J.W., H.-J.C., G.L., T.H., S.X., G.H., C.Y., F.L. and X.X. performed statistical analyses of the data sets and aided in the preparation of displays that communicated the data sets. J.W., M.X.W. and X.X. provided conceptual advice. M.X.W. and X.X. supervised the study. All the authors discussed the results and assisted in the preparation of the manuscript.

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Correspondence to Mei X. Wu or Xi Xie.

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Wang, J., Chen, HJ., Hang, T. et al. Physical activation of innate immunity by spiky particles. Nature Nanotech 13, 1078–1086 (2018). https://doi.org/10.1038/s41565-018-0274-0

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