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Regulating metalloimmunology with nanomedicine for cancer therapy

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Abstract

Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes (metalloproteins). Multiple aspects of the immune system, from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy, could be affected by metals. Therefore, the employment of metal for the regulation of immunity, termed as metalloimmunology, is gaining interest as a prevalent and efficacious approach to combating cancer. However, the manipulation of metalloimmunology using traditional drugs presents several challenges, including limited bioavailability, adverse effects, and a lack of targeting specificity. This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer. Essential trace metal elements, such as iron, zinc, copper, manganese, magnesium, and calcium, as well as heavy metal drugs and their mechanisms of action, will be discussed with a particular focus on their roles in regulating the tumor-immune interplay. The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed. These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.

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Acknowledgements

This work was supported by grants from the National Key R&D Program of China (Nos. 2021YFA1201100, and 2022YFA1206100), the National Natural Science Foundation of China (Nos. 32271449, 32201158, and 51773188), CAS Project for Young Scientists in Basic Research (No. YSBR-036), Key Project of Natural Science Foundation of Shandong Province (No. ZR2020KE016), Shandong Provincial Key Research and Development Program (Major Scientific and Technological Innovation Project, No. 2022CXGC010505).

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  1. Saibo Ma and Lin Chen contributed equally to this work.

Authors and Affiliations

  1. College of Marine Life Science, Ocean University of China, Qingdao, 266003, China

    Saibo Ma & Jing Chang

  2. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China

    Lin Chen, Muhammad Hamza & Motao Zhu

  3. Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266235, China

    Saibo Ma & Jing Chang

  4. University of Chinese Academy of Sciences, Beijing, 100049, China

    Motao Zhu

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  1. Saibo Ma
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  2. Lin Chen
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  3. Muhammad Hamza
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  4. Jing Chang
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  5. Motao Zhu
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Correspondence to Jing Chang or Motao Zhu.

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Ma, S., Chen, L., Hamza, M. et al. Regulating metalloimmunology with nanomedicine for cancer therapy. Nano Res. 16, 13164–13181 (2023). https://doi.org/10.1007/s12274-023-6212-y

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