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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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Zhang Q,Tao H,Lin Y,Hu Y,An H,Zhang D,Feng S,Hu H,Wang R,Li X,Zhang J

doi

10.1016/j.biomaterials.2016.08.010

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

206-221

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(16)30396-9

journal_volume

105

pub_type

杂志文章

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