Oxidation-Induced Degradable Nanogels for Iron Chelation

• Published in: Scientific reports Vol. 6; no. 1; p. 20923
• Main Authors: Liu, Zhi, Wang, Yan, Purro, Max, Xiong, May P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.02.2016; Nature Publishing Group
• Subjects: 639/925/352; 692/308/575; Absorption spectroscopy; Animals; Atomic absorption spectroscopy; Cadmium; Cell Death - drug effects; Cell Line; Chelation; Cytotoxicity; Deferoxamine; Deferoxamine - pharmacology; Dynamic Light Scattering; Ferritin; Ferrous Compounds - chemistry; Humanities and Social Sciences; Iron; Iron Chelating Agents - pharmacology; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Metallocenes; Mice; Microscopy, Electron, Transmission; multidisciplinary; Oxidation; Oxidation-Reduction; Oxidative stress; Polyethylene Glycols - chemistry; Polyethyleneimine - chemistry; Polymerization; Reactive oxygen species; Science; Spectroscopy; β-Cyclodextrin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20923

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.