Efficient Iron and ROS Nanoscavengers for Brain Protection after Intracerebral Hemorrhage

ACS Appl Mater Interfaces. 2021 Mar 3;13(8):9729-9738. doi: 10.1021/acsami.1c00491. Epub 2021 Feb 18.

Abstract

Intracerebral hemorrhage (ICH) will be accompanied by the overload of iron and reactive oxygen species (ROS) following hematoma clearance. Although deferoxamine (DFO) has been widely utilized as a clinical first-line siderophore to remove the iron overload, the ROS-inducing damage still greatly limits the therapeutic effect of DFO. To address this issue, we designed and fabricated a series of dual-functional macromolecular nanoscavengers featuring high-density DFO units and catechol moieties. Note that the former units could effectively remove the iron overload, while the latter ones could efficiently deplete the ROS. The resulting nanoscavengers efficiently down-regulate the iron and ROS levels as well as significantly reduce the cell death in both iron-overloaded RAW 264.7 cells and the ICH mice model. This work suggests a novel clue for the ICH-ameliorated iron-depleting interventional therapeutic regimen.

Keywords: brain protection; deferoxamine; intracerebral hemorrhage; nanoscavenger; poly(catechol).

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Catechols / chemical synthesis
  • Catechols / therapeutic use
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / physiopathology
  • Collagenases
  • Deferoxamine / analogs & derivatives
  • Deferoxamine / therapeutic use
  • Iron / metabolism
  • Iron Overload / drug therapy*
  • Iron Overload / etiology
  • Iron Overload / physiopathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / therapeutic use*
  • Polymers / chemical synthesis
  • Polymers / therapeutic use*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Siderophores / chemical synthesis
  • Siderophores / therapeutic use*

Substances

  • Antioxidants
  • Catechols
  • Neuroprotective Agents
  • Polymers
  • Reactive Oxygen Species
  • Siderophores
  • Iron
  • Collagenases
  • Deferoxamine