Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p-65 Signaling Pathway.
Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p-65 Signaling Pathway.
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DOI：
10.1002/advs.202206934
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发表时间：
2023-04
期刊：
影响因子：
--
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
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
慢性疼痛已引起人们的广泛关注，因为它是影响生活质量的主要障碍。因此，安全、高效和低成瘾性的药物是非常受欢迎的。纳米颗粒(NPs)具有强大的抗氧化应激和抗炎特性，具有治疗炎性疼痛的可能性。因此，开发了一种生物活性的沸石咪唑骨架(ZIF)-8-帽超氧化物歧化酶(SOD)和Fe3O4纳米粒子(SOD&Fe3O4@ZIF-8，SFZ)，以达到增强催化、抗氧化活性和炎症环境选择性的目的，最终改善镇痛效果。SFZ纳米粒可减少叔丁基氢过氧化氢(t-BOOH)诱导的活性氧(ROS)过量生成，从而抑制氧化应激，抑制脂多糖(LPS)诱导的小胶质细胞炎症反应。鞘内注射后，SFZ NPs在脊髓腰椎膨大处有效积聚，显著缓解完全弗氏佐剂(CFA)诱导的小鼠炎性疼痛。此外，进一步研究了SFZ NPs治疗炎性疼痛的详细机制，其中SFZ NPs抑制丝裂原活化蛋白激酶/p-65信号通路的激活，导致磷酸化蛋白水平(p-65、p-ERK、p-JNK和p-p38)和炎症因子(肿瘤坏死因子[肿瘤坏死因子]-α、白介素[IL]-6和IL-1β)的降低，从而阻止小胶质细胞和星形胶质细胞的止痛激活。本研究提供了一种用于抗氧化剂治疗的新型级联纳米酶，并探索了其作为非阿片类镇痛剂的潜在应用。将超氧化物歧化酶(SOD)和Fe3O4纳米颗粒包裹在分子筛咪唑骨架(ZIF)-8纳米颗粒中，制得了超氧化物歧化酶(SOD)和Fe3O4@ZIF-8(SFZ)纳米颗粒。鞘内注射SFZ纳米粒在弱酸性环境中降解，氧化应激、炎性细胞因子和丝裂原活化蛋白激酶/p-65信号通路被阻断，最终阻止胶质细胞激活，缓解炎性疼痛。
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 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. SOD&Fe3O4@ZIF‐8 (SFZ) nanoparticles (NPs), are obtained by encapsulating superoxide dismutase (SOD) and Fe3O4 NPs in zeolitic imidazolate framework (ZIF)‐8 NPs. SFZ NPs via intrathecal injection are degraded in a weakly acidic environment. Then, oxidative stress, inflammatory cytokines and the mitogen‐activated protein kinase/p‐65 signaling pathway is blocked, ultimately preventing the glial cell activation and relieving the inflammatory pain.
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影响因子：
5.1
作者：
Lin, Houmin;Dixon, Steven Grant;Hu, Wei;Hamlett, Eric D.;Jin, Junfei;Ergul, Adviye;Wang, Gavin Y.
通讯作者：
Wang, Gavin Y.
影响因子：
9.3
作者：
Dansereau MA;Midavaine É;Bégin-Lavallée V;Belkouch M;Beaudet N;Longpré JM;Mélik-Parsadaniantz S;Sarret P
通讯作者：
Sarret P
影响因子：
5.6
作者：
Liu, Tong;Gao, Yong-Jing;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
13.3
作者：
Kim, Tae Sung;Jin, Yeung Bae;Jo, Eun-Kyeong
通讯作者：
Jo, Eun-Kyeong
影响因子：
13.6
作者：
Cao, Chong;Huang, Juan;Yan, Chun-Ni
通讯作者：
Yan, Chun-Ni