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  • Review Article
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Engineering nanomaterial physical characteristics for cancer immunotherapy

Abstract

The physical properties of nanomaterials — such as size, structure, shape, charge, mechanical strength and hydrophobicity — can directly or indirectly influence immune cell functions and modulate immune responses in healthy and disease states. Therefore, nanomaterials can be designed with distinct physicochemical features for applications in immunobioengineering to achieve specific immunological effects. In this Review, we discuss how the physical features of natural and synthetic nanomaterials can affect protein adsorption, immune scavenging, biodistribution, immune cell targeting and toxicity. We highlight the nanoengineering advances that have enabled tailoring of the physical characteristics of nanomaterials for applications in cancer immunoengineering, and we outline the challenges in nanomaterials-based immunoengineering that need to be addressed to enable clinical translation.

Key points

  • Physical parameters modulate immune signalling pathways and effector functions in distinct immune cell subtypes such as dendritic cells, macrophages, T cells, natural killer cells and B cells.

  • Modulation of physical characteristics in nanomaterials affects their physiochemical properties, including biodistribution, pharmacokinetics, specific immune cell targeting or toxicity.

  • Engineering nanomaterial physical properties facilitates activation of antitumour immune signalling pathways and effector functions in distinct immune cell subtypes in a direct or indirect fashion.

  • The physical engineering of nanomaterials provides an unprecedented way to implement efficient cancer immunotherapy.

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Fig. 1: Physical factors influencing immunological functions in dendritic cells and macrophages.
Fig. 2: Physical attributes of nanomaterials affecting immunological functions of immune cells.
Fig. 3: Nanomaterial physical parameters modulate physiological effects.
Fig. 4: Physical features of nanomaterials regulate immune responses in cancer immunotherapy.
Fig. 5: Mechanical strength and multivalency of nanomaterials affect immunogenicity in cancer immunotherapy.

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Acknowledgements

This work was supported in part by the Cancer Center Support Center (Core) grant P30 CA016672 from the National Cancer Institute, National Institutes of Health. The authors thank C. F. Wogan for her assistance in editing various versions of the manuscript.

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D.Y.L., B.Y.S.K. and W.J. conceived this review, D.Y.L. wrote the manuscript and prepared the display items, and K.H., J.L., B.Y.S.K. and W.J. edited the manuscript. All authors read and approved the final version.

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Lee, D., Huntoon, K., Lux, J. et al. Engineering nanomaterial physical characteristics for cancer immunotherapy. Nat Rev Bioeng 1, 499–517 (2023). https://doi.org/10.1038/s44222-023-00047-3

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