Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy
Alzheimer's disease (AD), a global health crisis exacerbated by aging populations, demands innovative therapeutic strategies. Curcumin, a natural compound with anti-aging and anti-inflammatory properties, holds promise for AD treatment but is hindered by poor bioavailability. Here, we developed...
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Elsevier
2025-10-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007276 |
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| author | Jianjian Chu Hui Hu Wei Xu Xinyu Lu Honglei Zhou Mengqi Hao Li Wang Siqi Li Wenbo Ji Gang Li Yi Luo Jie Gao Dongya Huang Yan Liu You Yin |
| author_facet | Jianjian Chu Hui Hu Wei Xu Xinyu Lu Honglei Zhou Mengqi Hao Li Wang Siqi Li Wenbo Ji Gang Li Yi Luo Jie Gao Dongya Huang Yan Liu You Yin |
| author_sort | Jianjian Chu |
| collection | DOAJ |
| description | Alzheimer's disease (AD), a global health crisis exacerbated by aging populations, demands innovative therapeutic strategies. Curcumin, a natural compound with anti-aging and anti-inflammatory properties, holds promise for AD treatment but is hindered by poor bioavailability. Here, we developed curcumin-loaded nanovesicles (NV-CUR) derived from brain-homing B16 melanoma cells to overcome these limitations. NV-CUR enhanced the solubility, stability, and blood‒brain barrier (BBB) penetration of curcumin, enabling systemic delivery in aged 3 × Tg AD mice. Our 3R strategy for removing senescent cells, remodeling the neuroinflammatory microenvironment, and repairing neuronal damage was comprehensively validated. NV-CUR effectively cleared p16INK4a (P16)-positive senescent microglia, suppressed senescence-associated secretory phenotypes (SASP), and reduced neuroinflammation (IL-1β, IL-6, and TNF-α). Concurrently, NV-CUR diminished amyloid-beta plaques, attenuated Tau hyperphosphorylation, and restored hippocampal neuronal integrity. Cognitive assessments revealed significant improvements in memory and exploratory behavior, whereas biosafety evaluations confirmed that there was no systemic toxicity. This study establishes NV-CUR as a mechanistically innovative, clinically translatable nanomedicine that aligns with the 3R paradigm, offering a multifaceted approach to combat AD pathogenesis. |
| format | Article |
| id | doaj-art-28e8a7ab1b404d969a4d2d05c3ce15a8 |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-28e8a7ab1b404d969a4d2d05c3ce15a82025-08-20T03:02:36ZengElsevierMaterials Today Bio2590-00642025-10-013410215710.1016/j.mtbio.2025.102157Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapyJianjian Chu0Hui Hu1Wei Xu2Xinyu Lu3Honglei Zhou4Mengqi Hao5Li Wang6Siqi Li7Wenbo Ji8Gang Li9Yi Luo10Jie Gao11Dongya Huang12Yan Liu13You Yin14Department of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, China; Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China; Guigang Medical District, 923 Military Hospital of China, Guigang, ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, ChinaDepartment of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, ChinaDepartment of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, ChinaDepartment of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, ChinaDepartment of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaNew Drug Discovery and Development, Biotheus Inc, Zhuhai, China; Clinical pharmacy Innovation Institute, Shanghai Jiao Tong University of Medicine, Shanghai, China; Corresponding author. New Drug Discovery and Development, Biotheus Inc, Zhuhai, 519085, China.Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China; Corresponding author. Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, China.Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China; Corresponding author. Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Corresponding author. Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201600, China.Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China; Corresponding author. Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.Alzheimer's disease (AD), a global health crisis exacerbated by aging populations, demands innovative therapeutic strategies. Curcumin, a natural compound with anti-aging and anti-inflammatory properties, holds promise for AD treatment but is hindered by poor bioavailability. Here, we developed curcumin-loaded nanovesicles (NV-CUR) derived from brain-homing B16 melanoma cells to overcome these limitations. NV-CUR enhanced the solubility, stability, and blood‒brain barrier (BBB) penetration of curcumin, enabling systemic delivery in aged 3 × Tg AD mice. Our 3R strategy for removing senescent cells, remodeling the neuroinflammatory microenvironment, and repairing neuronal damage was comprehensively validated. NV-CUR effectively cleared p16INK4a (P16)-positive senescent microglia, suppressed senescence-associated secretory phenotypes (SASP), and reduced neuroinflammation (IL-1β, IL-6, and TNF-α). Concurrently, NV-CUR diminished amyloid-beta plaques, attenuated Tau hyperphosphorylation, and restored hippocampal neuronal integrity. Cognitive assessments revealed significant improvements in memory and exploratory behavior, whereas biosafety evaluations confirmed that there was no systemic toxicity. This study establishes NV-CUR as a mechanistically innovative, clinically translatable nanomedicine that aligns with the 3R paradigm, offering a multifaceted approach to combat AD pathogenesis.http://www.sciencedirect.com/science/article/pii/S2590006425007276Alzheimer's diseaseAgingCurcuminNanovesiclesblood‒brain barrier |
| spellingShingle | Jianjian Chu Hui Hu Wei Xu Xinyu Lu Honglei Zhou Mengqi Hao Li Wang Siqi Li Wenbo Ji Gang Li Yi Luo Jie Gao Dongya Huang Yan Liu You Yin Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy Materials Today Bio Alzheimer's disease Aging Curcumin Nanovesicles blood‒brain barrier |
| title | Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy |
| title_full | Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy |
| title_fullStr | Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy |
| title_full_unstemmed | Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy |
| title_short | Top-down engineered micron-cell derived nanovesicles encapsulating curcumin targeting the 3R strategy (remove, remodel, repair) for Alzheimer's disease therapy |
| title_sort | top down engineered micron cell derived nanovesicles encapsulating curcumin targeting the 3r strategy remove remodel repair for alzheimer s disease therapy |
| topic | Alzheimer's disease Aging Curcumin Nanovesicles blood‒brain barrier |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007276 |
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