Novel HOCl-ResponsiveTheranostic Prodrug for theEarly Diagnosis and Therapy of Ischemic Stroke

In this work, a hypochlorous acid (HOCl)-responsive prodrug <b>MB-R</b> for diagnosis and therapy of ischemic stroke (IS) was constructed using the near-infrared fluorophore methylene blue linked to riluzole by the urea bond. <b>MB-R</b> exhibits good biocompatibility, fast response (<1 min), and high selectivity toward HOCl. <b>MB-R</b> was successfully utilized to visualize the HOCl levels, as well as the distribution of HOCl in the brains of IS mice to determine the progression of the disease. Meanwhile, the treatment with <b>MB-R</b> could reduce the cerebral infarction volume and improve the motor function in IS mice. Most importantly, <b>MB-R</b> could be utilized in the treatment of stroke through antioxidant, anti-inflammatory, and neuroprotective effects, further suggesting that riluzole was a potentially therapeutic agent for IS. Thus, this work paves the way for the development of intelligent theranostic agent for the early diagnosis and treatment of IS.

Publication Details

Journal
Figshare
Published
2025-02-12
DOI
https://doi.org/10.1021/acs.jmedchem.4c03172.s001
Primary Topic
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
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article
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article

Novel HOCl-ResponsiveTheranostic Prodrug for theEarly Diagnosis and Therapy of Ischemic Stroke

Figshare
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
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Novel HOCl-ResponsiveTheranostic Prodrug for theEarly Diagnosis and Therapy of Ischemic Stroke

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Abstract

In this work, a hypochlorous acid (HOCl)-responsive prodrug <b>MB-R</b> for diagnosis and therapy of ischemic stroke (IS) was constructed using the near-infrared fluorophore methylene blue linked to riluzole by the urea bond. <b>MB-R</b> exhibits good biocompatibility, fast response (<1 min), and high selectivity toward HOCl. <b>MB-R</b> was successfully utilized to visualize the HOCl levels, as well as the distribution of HOCl in the brains of IS mice to determine the progression of the disease. Meanwhile, the treatment with <b>MB-R</b> could reduce the cerebral infarction volume and improve the motor function in IS mice. Most importantly, <b>MB-R</b> could be utilized in the treatment of stroke through antioxidant, anti-inflammatory, and neuroprotective effects, further suggesting that riluzole was a potentially therapeutic agent for IS. Thus, this work paves the way for the development of intelligent theranostic agent for the early diagnosis and treatment of IS.

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Neutrophil, Myeloperoxidase and Oxidative Mechanisms
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