Dataset Information

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 ?-cyclodextrin (?-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.

SUBMITTER: Liu Z

PROVIDER: S-EPMC4751432 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Oxidation-Induced Degradable Nanogels for Iron Chelation.

Liu Zhi Z Wang Yan Y Purro Max M Xiong May P MP

Scientific reports 20160212

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 m ...[more]

PMID: 26868174

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Project description:Liver fibrosis is a hard-to-treat disease with liver transplantation as only effective curation to this date. During disease progression, immune suppressive macrophages dominate and support fibrosis formation by replacement of functional parenchyma with collagen-dominating scare tissue. To alter the macrophage behavior, a pH-degradable, nanogel-based delivery system was developed for the covalent conjugation of the clinically approved bisphosphonate alendronate. The nanocarrier mediates the drugs’ delivery into hepatic nonparenchymal cells after intravenous administration and, thereby, triggers a macrophage repolarization against fibrosis progression. This approach may provide a significant contribution to establish further nanotherapeutic delivery strategies to effectively treat liver fibrosis. Immune suppressive macrophages contribute to the progression of several diseases including cancer and fibrosis. Especially in chronically damaged liver tissues they trigger the replacement of functional parenchyma by collagen-dominating scare tissue. In this study, we aimed to intervene into this cascade by repolarizing the macrophage phenotype via a pH-degradable, squaric ester-based nanogel carrier system. This nanotechnology platform enables a selective covalent conjugation of the highly water-soluble bisphosphonate alendronate and, thus, its safe and efficient delivery to hepatic nonparenchymal cells of fibrotic livers after intravenous administration. The bisphosphonate triggers a reprogramming of profibrotic M2- towards antifibrotic M1-phenotype macrophages affording an fibrolytic outcome, as verified both on mRNA and protein level. Further insights by genomic and proteomic studies confirm the macrophages’ repolarization and thus corroborate the virtue of the nanogels as biocompatible nanocarrier platform for hepatotropic bisphosphonate delivery. Beyond preventing liver fibrosis progression, these nanogels may therefore represent an attractive device for further nanotherapeutic interventions in M2-type macrophage dominating diseases.

Dataset Information

Oxidation-Induced Degradable Nanogels for Iron Chelation.

Publications

Oxidation-Induced Degradable Nanogels for Iron Chelation.

Similar Datasets

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