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Papers of the Week

Papers: 18 Feb 2023 - 24 Feb 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development


2023 Feb 17

Adv Sci (Weinh)


Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p-65 Signaling Pathway.


Ling Y, Nie D, Huang Y, Deng M, Liu Q, Shi J, Ouyang S, Yang Y, Deng S, Lu Z, Yang J, Wang Y, Huang R, Shi W


Chronic 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 Fe O NPs (SOD&Fe O @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.