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- W2897289019 abstract "Copper deficiency is implicated in a variety of genetic, neurological, cardiovascular, and metabolic diseases. Current approaches for addressing copper deficiency rely on generic copper supplementation, which can potentially lead to detrimental off-target metal accumulation in unwanted tissues and subsequently trigger oxidative stress and damage cascades. Here we present a new modular platform for delivering metal ions in a tissue-specific manner and demonstrate liver-targeted copper supplementation as a proof of concept of this strategy. Specifically, we designed and synthesized an N-acetylgalactosamine-functionalized ionophore, Gal-Cu(gtsm), to serve as a copper-carrying “Trojan Horse” that targets liver-localized asialoglycoprotein receptors (ASGPRs) and releases copper only after being taken up by cells, where the reducing intracellular environment triggers copper release from the ionophore. We utilized a combination of bioluminescence imaging and inductively coupled plasma mass spectrometry assays to establish ASGPR-dependent copper accumulation with this reagent in both liver cell culture and mouse models with minimal toxicity. The modular nature of our synthetic approach presages that this platform can be expanded to deliver a broader range of metals to specific cells, tissues, and organs in a more directed manner to treat metal deficiency in disease." @default.
- W2897289019 created "2018-10-26" @default.
- W2897289019 creator A5009857673 @default.
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- W2897289019 creator A5075325105 @default.
- W2897289019 date "2018-10-15" @default.
- W2897289019 modified "2023-10-09" @default.
- W2897289019 title "A Modular Ionophore Platform for Liver-Directed Copper Supplementation in Cells and Animals" @default.
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- W2897289019 doi "https://doi.org/10.1021/jacs.8b08014" @default.
- W2897289019 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6465169" @default.
- W2897289019 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30351140" @default.
- W2897289019 hasPublicationYear "2018" @default.
- W2897289019 type Work @default.