title: Oxidation-Induced Degradable Nanogels for Iron Chelation.
abstract: Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison 777 Highland Avenue, Madison, WI 53705-2222, USA.
authors: Zhi
authors: Z
authors: Liu
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison 777 Highland Avenue, Madison, WI 53705-2222, USA.
authors: Yan
authors: Y
authors: Wang
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison 777 Highland Avenue, Madison, WI 53705-2222, USA.
authors: Max
authors: M
authors: Purro
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison 777 Highland Avenue, Madison, WI 53705-2222, USA.
authors: May P
authors: MP
authors: Xiong
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003676:Deferoxamine / Q000494:pharmacology; D000067493:Dynamic Light Scattering; D005296:Ferrous Compounds / Q000737:chemistry; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D000075163:Metallocenes; D051379:Mice; D046529:Microscopy, Electron, Transmission; D000080385:Nanogels; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D058105:Polymerization
chemical_list: D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D000075163:Metallocenes; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D003676:Deferoxamine; C004998:ferrocene