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ROS-triggered degradable iron-chelating nanogels: Safely improving iron elimination in vivo.

ABSTRACT: Iron-mediated generation of highly toxic Reactive Oxygen Species (ROS) plays a major role in the process leading to iron overload-related diseases. The long-term subcutaneous administration of Deferoxamine (DFO) is currently clinically-approved to improve patient symptoms and survival. However, non-specific toxicity and short circulation times of the drug in humans often leads to poor patient compliance. Herein, thioketal-based ROS-responsive polymeric nanogels containing DFO moieties (rNG-DFO) were designed to chelate iron and to degrade under oxidative stimuli into fragments <10?nm to enhance excretion of iron-bound chelates. Serum ferritin levels and iron concentrations in major organs of IO mice decreased following treatment with rNG-DFO, and fecal elimination of iron-bound chelates increased compared to free DFO. Furthermore, rNG-DFO decreased iron mediated oxidative stress levels in vitro and reduced iron-mediated inflammation in the liver of IO mice. The study confirms that ROS-responsive nanogels may serve as a promising alternative to DFO for safer and more efficient iron chelation therapy.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6035766 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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ROS-triggered degradable iron-chelating nanogels: Safely improving iron elimination in vivo.

Liu Zhi Z Qiao Jing J Nagy Tamas T Xiong May P MP

Journal of controlled release : official journal of the Controlled Release Society 20180522

Iron-mediated generation of highly toxic Reactive Oxygen Species (ROS) plays a major role in the process leading to iron overload-related diseases. The long-term subcutaneous administration of Deferoxamine (DFO) is currently clinically-approved to improve patient symptoms and survival. However, non-specific toxicity and short circulation times of the drug in humans often leads to poor patient compliance. Herein, thioketal-based ROS-responsive polymeric nanogels containing DFO moieties (rNG-DFO) ...[more]

PMID: 29792889

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Dataset Information

ROS-triggered degradable iron-chelating nanogels: Safely improving iron elimination in vivo.

Publications

ROS-triggered degradable iron-chelating nanogels: Safely improving iron elimination in vivo.

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