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  • Review Article
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Regulating trained immunity with nanomedicine

Nature Reviews Materials volume 7, pages 465–481 (2022) Cite this article

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Abstract

Trained immunity refers to a hyperresponsive functional state of the innate immune system, which is induced by certain stimuli, such as infections or vaccination. Trained immunity plays a key part in a variety of diseases, including cancer and inflammation, and is regulated through epigenetic and metabolic reprogramming of haematopoietic stem and progenitor cells in the bone marrow, giving rise to hyperactive myeloid cells. Nanomaterials inherently interact with phagocytic myeloid cells and are thus ideal platforms with which to regulate trained immunity. In this Review, we discuss the key pathways of trained immunity and investigate nanomedicine strategies to therapeutically regulate trained immunity. Nanomedicine can be applied not only to induce trained immunity to treat cancer or to enhance resistance to infections, but also to manage hyperinflammation and maladaptive trained immunity in a variety of clinical scenarios. We conclude with an outlook to future possibilities and some remaining challenges for nanomedicine approaches in trained immunity regulation.

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Fig. 1: Trained immunity targeting levels.
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Fig. 2: The journey of nanomaterials upon intravenous administration.
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Fig. 3: Nanoparticle platforms.
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Fig. 4: Trained-immunity-regulating nanotherapies in clinical scenarios.
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Fig. 5: Applications of nanoimmunotherapies.
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Fig. 6: Translation from preclinical concept to clinical trials.
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Acknowledgements

This work was supported by National Institutes of Health (NIH) grants R01 HL144072, R01 CA220234, and P01 HL131478, as well as a Vici grant from the Dutch Research Council NWO and a European Research Council (ERC) Advanced Grant (no. 101019807) (all to W.J.M.M.). M.G.N. was supported by a Spinoza grant from the Netherlands Organization for Scientific Research and an ERC Advanced Grant (no. 833247).

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Authors and Affiliations

  1. BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Mandy M. T. van Leent & Bram Priem

  2. Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Mandy M. T. van Leent & Bram Priem

  3. Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Mandy M. T. van Leent

  4. Angiogenesis Laboratory, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, Netherlands

    Bram Priem

  5. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

    David P. Schrijver, Anne de Dreu, Stijn R. J. Hofstraat, Robby Zwolsman & Willem J. M. Mulder

  6. Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

    Thijs J. Beldman, Mihai G. Netea & Willem J. M. Mulder

  7. Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, Netherlands

    Mihai G. Netea

  8. Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany

    Mihai G. Netea

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M.M.T.v.L., B.P. and W.J.M.M. wrote the manuscript. All authors researched data for the article, provided substantial contributions to discussion of content and reviewed and edited the manuscript before submission.

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Correspondence to Mihai G. Netea or Willem J. M. Mulder.

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W.J.M.M. and M.G.N. are scientific founders and shareholders of Trained Therapeutix Discovery.

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Nature Reviews Materials thanks Angus Johnston and the other, anonymous, reviewers for their contribution to the peer review of this work.

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van Leent, M.M.T., Priem, B., Schrijver, D.P. et al. Regulating trained immunity with nanomedicine. Nat Rev Mater 7, 465–481 (2022). https://doi.org/10.1038/s41578-021-00413-w

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