title: A superoxide dismutase/catalase mimetic nanomedicine for targeted therapy of inflammatory bowel disease.
abstract: Oxidative stress, resulting from excessive generation of reactive oxygen species (ROS), plays a pivotal role in the initiation and progression of inflammatory bowel disease (IBD). To develop an efficacious and safe nanotherapy against IBD, we designed and developed a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger Tempol (Tpl). To this end, an oxidation-responsive β-cyclodextrin material (OxbCD) was synthesized, and a Tpl-loaded OxbCD nanoparticle (Tpl/OxbCD NP) was produced. Hydrolysis of OxbCD NP could be triggered by hydrogen peroxide, leading to on-demand release of loaded Tpl molecules from Tpl/OxbCD NP. OxbCD NP was able to efficiently accumulate in the inflamed colon in mice, thereby dramatically reducing nonspecific distribution after oral delivery. In three mouse colitis models, oral administration of Tpl/OxbCD NP notably mitigated manifestations relevant to colitis, and significantly suppressed expression of proinflammatory mediators, with the efficacy superior over free Tpl or a control nanomedicine based on poly(lactide-co-glycolide) (PLGA). Accordingly, by scavenging multiple components of ROS, Tpl/OxbCD NP may effectively reduce ulcerative colitis in mice, and it can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China; Institute of Materia Medica, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China.
authors.forename: Qixiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China.
authors.forename: Yongyao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: An
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China; Department of Chemistry, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Dinglin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Shibin
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Houyuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China. Electronic address: lpsh008@aliyun.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, 30 Gaotanyan Main St., Chongqing, 400038, China. Electronic address: jxzhang1980@gmail.com.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry; D040761:Biomimetic Materials / Q000008:administration & dosage / Q000737:chemistry; D002374:Catalase / Q000008:administration & dosage / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy / Q000379:methods*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D013113:Spin Labels; D002374:Catalase; D013482:Superoxide Dismutase; C001803:tempol
keywords: Colitis; Cyclodextrin; Drug delivery; Reactive oxygen species; Responsive nanoparticles; Targeted therapy