Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 8, Pages 9729-9738Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c00491
Keywords
deferoxamine; poly(catechol); nanoscavenger; brain protection; intracerebral hemorrhage
Funding
- National Natural Science Foundation of China [81401528]
- 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZY2016102, ZY2016203]
- Program of the Science & Technology Department of Guangzhou, China [201803020039]
- Fundamental Research Funds for Central Universities
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Novel dual-functional macromolecular nanoscavengers designed in this study can efficiently remove iron and ROS, reducing cell death caused by iron overload. This provides a new direction for improving therapeutic strategies for ICH.
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.
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