title: Synthesis and evaluation of oxidation-responsive alginate-deferoxamine conjugates with increased stability and low toxicity.
abstract: Deferoxamine is commonly used for iron-overload related diseases, its drawbacks such as instability and toxicity, however, significantly limited its utility in clinic. To address these issues, oxidation-responsive alginate-deferoxamine (Alg-DFO) conjugates were synthesized and their structure was characterized. The metabolism studies shown the conjugation of alginate significantly increased the stability of the DFO, with half-life more than 10 times longer than that of the free DFO. Moreover, the conjugates could not only quickly respond to oxidative stimuli and degradation, suggesting their potential to be cleared from the body by responding to iron-overload associated oxidative environment to avoid its accumulation and safety concern, but also protect iron binding capacity of the attached DFO from oxidation. The degradation mechanism for oxidative-response was proposed. In addition, the conjugates shown lower cytotoxicity compared to the free DFO. Taken together, the Alg-DFO conjugates synthesized in this work has promise for treating iron-overload related conditions.
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: tianmong007@gmail.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China; State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: Youchao@vip.126.com.
authors.forename: Chao
authors.initials: C
authors.lastname: You
mesh_terms: D000464:Alginates / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003676:Deferoxamine / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004355:Drug Stability; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D008970:Molecular Weight; D010084:Oxidation-Reduction; D014867:Water / Q000737:chemistry
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D014867:Water; D020723:Glucuronic Acid; D007501:Iron; D003676:Deferoxamine
keywords: Alginate; Deferoxamine; Oxidation response; Stability; Toxicity