Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes

Abstract Traumatic brain injury (TBI) disrupts oxygen homeostasis in the brain, leading to excessive reactive oxygen species (ROS) production and dysregulated antioxidant mechanisms, which fail to clear excess ROS. This ROS overload promotes the expression of pro-inflammatory genes, releasing cytoki...

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Main Authors: Xianhua Fu, Yongkang Zhang, Guojie Chen, Guangyao Mao, Jiajia Tang, Jin Xu, Yuhan Han, Honglin Chen, Lianshu Ding
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-025-03251-y
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author Xianhua Fu
Yongkang Zhang
Guojie Chen
Guangyao Mao
Jiajia Tang
Jin Xu
Yuhan Han
Honglin Chen
Lianshu Ding
author_facet Xianhua Fu
Yongkang Zhang
Guojie Chen
Guangyao Mao
Jiajia Tang
Jin Xu
Yuhan Han
Honglin Chen
Lianshu Ding
author_sort Xianhua Fu
collection DOAJ
description Abstract Traumatic brain injury (TBI) disrupts oxygen homeostasis in the brain, leading to excessive reactive oxygen species (ROS) production and dysregulated antioxidant mechanisms, which fail to clear excess ROS. This ROS overload promotes the expression of pro-inflammatory genes, releasing cytokines and chemokines and creating a vicious “ROS-neuroinflammation” cycle, making it essential to break this cycle for effective TBI treatment. In this study, we developed cysteine-alanine-glutamine-lysine (CAQK) peptide-modified antioxidant nanoparticles (C-PPS/C) for co-delivery of curcumin (Cur) to modulate oxidative and neuroinflammatory disturbances after TBI. In TBI mice, C-PPS/C nanoparticles accumulated in injured brain regions, where poly (propylene sulfide)120 scavenged ROS, reducing oxidative stress, while Cur release further suppressed ROS and inflammation. C-PPS/C nanoparticles broke the “ROS-neuroinflammation” cycle, protecting the blood-brain barrier (BBB), reducing acute brain edema, and promoting long-term neurological recovery. Further investigation showed that C-PPS/C nanoparticles inhibited the NF-κB pathway, reducing pro-inflammatory gene expression and mitigating inflammation, suggesting a promising approach for TBI treatment.
format Article
id doaj-art-3619bcad44a849eabb7b4d0be41a3f24
institution OA Journals
issn 1477-3155
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publishDate 2025-03-01
publisher BMC
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series Journal of Nanobiotechnology
spelling doaj-art-3619bcad44a849eabb7b4d0be41a3f242025-08-20T01:57:51ZengBMCJournal of Nanobiotechnology1477-31552025-03-0123112210.1186/s12951-025-03251-yResponsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomesXianhua Fu0Yongkang Zhang1Guojie Chen2Guangyao Mao3Jiajia Tang4Jin Xu5Yuhan Han6Honglin Chen7Lianshu Ding8Department of Neurosurgery, The Affiliated Huaian NO.1 People’s Hospital of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital of Xuzhou Medical UniversityClinical Laboratory, Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityClinical Laboratory, Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversityBrain Injury Center, Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Neurosurgery, The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversityDepartment of Neurosurgery, The Affiliated Huaian NO.1 People’s Hospital of Nanjing Medical UniversityAbstract Traumatic brain injury (TBI) disrupts oxygen homeostasis in the brain, leading to excessive reactive oxygen species (ROS) production and dysregulated antioxidant mechanisms, which fail to clear excess ROS. This ROS overload promotes the expression of pro-inflammatory genes, releasing cytokines and chemokines and creating a vicious “ROS-neuroinflammation” cycle, making it essential to break this cycle for effective TBI treatment. In this study, we developed cysteine-alanine-glutamine-lysine (CAQK) peptide-modified antioxidant nanoparticles (C-PPS/C) for co-delivery of curcumin (Cur) to modulate oxidative and neuroinflammatory disturbances after TBI. In TBI mice, C-PPS/C nanoparticles accumulated in injured brain regions, where poly (propylene sulfide)120 scavenged ROS, reducing oxidative stress, while Cur release further suppressed ROS and inflammation. C-PPS/C nanoparticles broke the “ROS-neuroinflammation” cycle, protecting the blood-brain barrier (BBB), reducing acute brain edema, and promoting long-term neurological recovery. Further investigation showed that C-PPS/C nanoparticles inhibited the NF-κB pathway, reducing pro-inflammatory gene expression and mitigating inflammation, suggesting a promising approach for TBI treatment.https://doi.org/10.1186/s12951-025-03251-yTraumatic brain injuryCurcuminReactive oxygen speciesNeuroinflammationNF-κB
spellingShingle Xianhua Fu
Yongkang Zhang
Guojie Chen
Guangyao Mao
Jiajia Tang
Jin Xu
Yuhan Han
Honglin Chen
Lianshu Ding
Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes
Journal of Nanobiotechnology
Traumatic brain injury
Curcumin
Reactive oxygen species
Neuroinflammation
NF-κB
title Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes
title_full Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes
title_fullStr Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes
title_full_unstemmed Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes
title_short Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes
title_sort responsive nanoparticles synergize with curcumin to break the reactive oxygen species neuroinflammation vicious cycle enhancing traumatic brain injury outcomes
topic Traumatic brain injury
Curcumin
Reactive oxygen species
Neuroinflammation
NF-κB
url https://doi.org/10.1186/s12951-025-03251-y
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