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Metabolic glycan labelling for cancer-targeted therapy

Nature Chemistry volume 12, pages 1102–1114 (2020)Cite this article

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Abstract

Metabolic glycoengineering with unnatural sugars provides a powerful tool to label cell membranes with chemical tags for subsequent targeted conjugation of molecular cargos via efficient chemistries. This technology has been widely explored for cancer labelling and targeting. However, as this metabolic labelling process can occur in both cancerous and normal cells, cancer-selective labelling needs to be achieved to develop cancer-targeted therapies. Unnatural sugars can be either rationally designed to enable preferential labelling of cancer cells, or specifically delivered to cancerous tissues. In this Review Article, we will discuss the progress to date in design and delivery of unnatural sugars for metabolic labelling of tumour cells and subsequent development of tumour-targeted therapy. Metabolic cell labelling for cancer immunotherapy will also be discussed. Finally, we will provide a perspective on future directions of metabolic labelling of cancer and immune cells for the development of potent, clinically translatable cancer therapies.

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Fig. 1: Metabolic labelling of cancer cells with reactive chemical tags via unnatural monosaccharides.
Fig. 2: Materials for systemic delivery of unnatural sugars to tumours.
Fig. 3: Rational design of unnatural sugars with cancer-labelling selectivity.
Fig. 4: Metabolic labelling of cancer cells for cancer-targeted treatment.
Fig. 5: Metabolic sugar labelling for cancer immunotherapy.

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Acknowledgements

This work was supported by funding from National Institutes of Health (1 R01 EB023287, 1 R01 CA223255). H.W. gratefully acknowledges funding support from the Wyss Technology Development Fellowship.

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  1. Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Hua Wang & David J. Mooney

  2. Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, USA

    Hua Wang & David J. Mooney

  3. Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Hua Wang

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H.W. and D.J.M. discussed and wrote the manuscript. We also would like to thank Alexander Najibi, Miguel Sobral, and Alberto Elósegui for insightful comments on the manuscript.

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Correspondence to David J. Mooney.

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Wang, H., Mooney, D.J. Metabolic glycan labelling for cancer-targeted therapy. Nat. Chem. 12, 1102–1114 (2020). https://doi.org/10.1038/s41557-020-00587-w

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