Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease
Abstract Antioxidant enzyme therapy shows promise for treating Alzheimer’s disease (AD), but significant challenges remain in achieving effective blood–brain barrier (BBB) penetration and sustained therapeutic effects. We developed a novel neutrophil membrane (NM)-coated cerium-doped Prussian blue b...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03263-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850072237049118720 |
|---|---|
| author | Jing Ma Yu Tian Chengzhong Du Yang Zhu Wen Huang Chenyu Ding Penghui Wei Xuehan Yi Zhangya Lin Wenhua Fang |
| author_facet | Jing Ma Yu Tian Chengzhong Du Yang Zhu Wen Huang Chenyu Ding Penghui Wei Xuehan Yi Zhangya Lin Wenhua Fang |
| author_sort | Jing Ma |
| collection | DOAJ |
| description | Abstract Antioxidant enzyme therapy shows promise for treating Alzheimer’s disease (AD), but significant challenges remain in achieving effective blood–brain barrier (BBB) penetration and sustained therapeutic effects. We developed a novel neutrophil membrane (NM)-coated cerium-doped Prussian blue biomimetic nanozyme (NM@PB-Ce) that demonstrates outstanding enzymatic properties and targeted therapeutic efficacy. Extensive physicochemical characterization using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering confirmed the successful synthesis of uniform nanoparticles (~ 142 nm) with preserved membrane protein functionality. In vitro studies utilizing SH-SY5Y neuroblastoma cells revealed that NM@PB-Ce effectively scavenged reactive oxygen species through multiple enzyme-mimetic activities (catalase, superoxide dismutase, and peroxidase). The nanozyme significantly suppressed NLRP3 inflammasome activation and subsequent pyroptosis, reducing inflammatory markers (IL-1β, IL-18) while attenuating Aβ aggregation. Using a sophisticated co-culture BBB model and real-time in vivo fluorescence imaging, we demonstrated NM@PB-Ce’s ability to traverse the BBB and accumulate specifically in AD-affected regions. In an Aβ1-42 oligomer-induced AD mouse model, systematic administration of NM@PB-Ce (320 μg/mL, 0.01 mL/g/day for 14 days) significantly improved cognitive performance across multiple behavioral paradigms, including the Morris water maze, Y-maze, and open field tests. Molecular and histological analyses revealed decreased neuroinflammation markers (GFAP, Iba-1) in the hippocampus, reduced levels of NLRP3, caspase-1, and phosphorylated tau (demonstrated by Western blot and ELISA), and enhanced dendritic spine density (visualized through Golgi staining). This comprehensive study establishes NM@PB-Ce as a promising therapeutic platform for AD treatment, providing both mechanistic insights into its mode of action and robust evidence of its therapeutic efficacy in targeting neuroinflammation and cognitive decline. Graphical Abstract |
| format | Article |
| id | doaj-art-44a05413cd334b6e88e90cd73639bac9 |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-44a05413cd334b6e88e90cd73639bac92025-08-20T02:47:07ZengBMCJournal of Nanobiotechnology1477-31552025-03-0123112210.1186/s12951-025-03263-8Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s diseaseJing Ma0Yu Tian1Chengzhong Du2Yang Zhu3Wen Huang4Chenyu Ding5Penghui Wei6Xuehan Yi7Zhangya Lin8Wenhua Fang9Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Fujian Medical University Union HospitalDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityAbstract Antioxidant enzyme therapy shows promise for treating Alzheimer’s disease (AD), but significant challenges remain in achieving effective blood–brain barrier (BBB) penetration and sustained therapeutic effects. We developed a novel neutrophil membrane (NM)-coated cerium-doped Prussian blue biomimetic nanozyme (NM@PB-Ce) that demonstrates outstanding enzymatic properties and targeted therapeutic efficacy. Extensive physicochemical characterization using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering confirmed the successful synthesis of uniform nanoparticles (~ 142 nm) with preserved membrane protein functionality. In vitro studies utilizing SH-SY5Y neuroblastoma cells revealed that NM@PB-Ce effectively scavenged reactive oxygen species through multiple enzyme-mimetic activities (catalase, superoxide dismutase, and peroxidase). The nanozyme significantly suppressed NLRP3 inflammasome activation and subsequent pyroptosis, reducing inflammatory markers (IL-1β, IL-18) while attenuating Aβ aggregation. Using a sophisticated co-culture BBB model and real-time in vivo fluorescence imaging, we demonstrated NM@PB-Ce’s ability to traverse the BBB and accumulate specifically in AD-affected regions. In an Aβ1-42 oligomer-induced AD mouse model, systematic administration of NM@PB-Ce (320 μg/mL, 0.01 mL/g/day for 14 days) significantly improved cognitive performance across multiple behavioral paradigms, including the Morris water maze, Y-maze, and open field tests. Molecular and histological analyses revealed decreased neuroinflammation markers (GFAP, Iba-1) in the hippocampus, reduced levels of NLRP3, caspase-1, and phosphorylated tau (demonstrated by Western blot and ELISA), and enhanced dendritic spine density (visualized through Golgi staining). This comprehensive study establishes NM@PB-Ce as a promising therapeutic platform for AD treatment, providing both mechanistic insights into its mode of action and robust evidence of its therapeutic efficacy in targeting neuroinflammation and cognitive decline. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03263-8NanozymeAlzheimer’s diseasePyroptosisReactive oxygen speciesNeuroinflammation |
| spellingShingle | Jing Ma Yu Tian Chengzhong Du Yang Zhu Wen Huang Chenyu Ding Penghui Wei Xuehan Yi Zhangya Lin Wenhua Fang Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease Journal of Nanobiotechnology Nanozyme Alzheimer’s disease Pyroptosis Reactive oxygen species Neuroinflammation |
| title | Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease |
| title_full | Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease |
| title_fullStr | Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease |
| title_full_unstemmed | Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease |
| title_short | Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer’s disease |
| title_sort | cerium doped prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate aβ oligomer induced neurotoxicity in alzheimer s disease |
| topic | Nanozyme Alzheimer’s disease Pyroptosis Reactive oxygen species Neuroinflammation |
| url | https://doi.org/10.1186/s12951-025-03263-8 |
| work_keys_str_mv | AT jingma ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT yutian ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT chengzhongdu ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT yangzhu ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT wenhuang ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT chenyuding ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT penghuiwei ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT xuehanyi ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT zhangyalin ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease AT wenhuafang ceriumdopedprussianbluebiomimeticnanozymeasanamplifiedpyroptosisinhibitormitigateaboligomerinducedneurotoxicityinalzheimersdisease |