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Chemical Modulation of in vivo Macrophage Function with Subpopulation-Specific Fluorescent Prodrug Conjugates

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Original languageEnglish
Pages (from-to)995-1005
Number of pages11
JournalACS central science
Volume3
Issue number9
Early online date30 Aug 2017
DOIs
Publication statusPublished - 27 Sep 2017

Abstract

Immunomodulatory agents represent one of the most promising strategies for enhancing tissue regeneration without the side effects of traditional drug-based therapies. Tissue repair depends largely on macrophages, making them ideal targets for pro-regenerative therapies. However, given the multiple roles of macrophages in tissue homeostasis, small molecule drugs must be only active in very specific subpopulations. In this work, we have developed the first prodrug-fluorophore conjugates able to discriminate closely-related subpopulations of macrophages (i.e. pro-inflammatory M1 vs. anti-inflammatory M2 macrophages), and employed them to deplete M1 macrophages in vivo without affecting other cell populations. Selective intracellular activation and drug release enabled simultaneous fluorescence cell tracking and ablation of M1 macrophages in vivo, with the concomitant rescue of a pro-regenerative phenotype. Ex vivo assays in human monocyte-derived macrophages validate the translational potential of this novel platform to develop chemical immunomodulatory agents as targeted therapies for immune-related diseases.

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