Affiliation:
1. Department of Neurosurgery Research Center of Clinical Medicine Neuro‐Microscopy and Minimally Invasive Translational Medicine Innovation Center Affiliated Hospital of Nantong University Medical School of Nantong University Nantong University 226001 Nantong P. R. China
2. Institute of Pain Medicine and Special Environmental Medicine Nantong University Nantong 226001 P. R. China
3. Department of Neurosurgery Yancheng First Hospital Affiliated Hospital of Nanjing University Medical School The First people's Hospital of Yancheng 224001 Yancheng P. R. China
4. Center for Advanced Low‐dimension Materials State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Chemistry Chemical Engineering and Biotechnology Donghua University Shanghai 201620 P. R. China
5. Department of Pharmaceutics School of Pharmacy Key Laboratory of Smart Drug Delivery Ministry of Education Fudan University Shanghai 215537 P. R. China
Abstract
AbstractChronic pain has attracted wide interest because it is a major obstacle affecting the quality of life. Consequently, safe, efficient, and low‐addictive drugs are highly desirable. Nanoparticles (NPs) with robust anti‐oxidative stress and anti‐inflammatory properties possess therapeutic possibilities for inflammatory pain. Herein, a bioactive zeolitic imidazolate framework (ZIF)‐8‐capped superoxide dismutase (SOD) and Fe3O4 NPs (SOD&Fe3O4@ZIF‐8, SFZ) is developed to achieve enhanced catalytic, antioxidative activities, and inflammatory environment selectivity, ultimately improving analgesic efficacy. SFZ NPs reduce tert‐butyl hydroperoxide (t‐BOOH)‐induced reactive oxygen species (ROS) overproduction, thereby depressing the oxidative stress and inhibiting the lipopolysaccharide (LPS)‐induced inflammatory response in microglia. After intrathecal injection, SFZ NPs efficiently accumulate at the lumbar enlargement of the spinal cord and significantly relieve complete Freund's adjuvant (CFA)‐induced inflammatory pain in mice. Moreover, the detailed mechanism of inflammatory pain therapy via SFZ NPs is further studied, where SFZ NPs inhibit the activation of the mitogen‐activated protein kinase (MAPK)/p‐65 signaling pathway, leading to reductions in phosphorylated protein levels (p‐65, p‐ERK, p‐JNK, and p‐p38) and inflammatory factors (tumor necrosis factor [TNF]‐α, interleukin [IL]‐6, and IL‐1β), thereby preventing microglia and astrocyte activation for acesodyne. This study provides a new cascade nanoenzyme for antioxidant treatments and explores its potential applications as non‐opioid analgesics.
Funder
National Natural Science Foundation of China
Program of Shanghai Academic Research Leader
Natural Science Foundation of Shanghai
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
7 articles.
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