Omnidirectional improvement of mitochondrial health in Alzheimer's disease by multi-targeting engineered activated neutrophil exosomes
Open accessAbstract
Alzheimer's disease (AD) is one kind of devasting neurodegenerative disorders affecting over 50 million people worldwide. Multi-targeted therapy has emerged as a new treatment for diagnosing and alleviating the pathogenesis process of AD; however, the current strategy is limited by its unsatisfactory efficiency. In our study, engineered activated neutrophil-derived exosomes (MP@Cur-MExo) were developed to improve the mitochondrial function in neurons by targeting and alleviating Aβ-induced neurotoxicity. MP@Cur-MExo are exosomes derived from IL-8-stimulated neutrophils decorated with mitochondria targeting ligand and Aβ targeted ligand modified SPION. Engineered exosomes can be cleaved by matrix metallopeptidase-2, which is overexpressed in the AD brain. Consequently, the released SPION and Curcumin-loaded engineered exosomes collaboratively protected neuron cells against Aβ-induced mitochondrial deficiency. In addition, MP@Cur-MExo effectively accumulated in the inflamed region of AD brain at an early stage, allowing early diagnosis of AD through bimodal (MRI/IVIS) imaging. Importantly, in a mouse model at an early stage of AD, intravenously injected MP@Cur-MExo restored mitochondrial function and reduced Aβ-induced mitochondrial damage, thereby attenuating AD progression. In conclusion, our designed engineered exosomes demonstrated that omnidirectional improvement of mitochondrial function can serve as a novel and practical approach for the diagnosis and treatment of neurodegenerative diseases. This study also reveals a promising therapeutic agent for impeding AD progression for future clinical applications.
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A number of studies employ multimodal approaches, combining MRI with PET, SPECT, or fluorescence imaging, which compensates for the limitations of each method individually.
“A number of studies employ multimodal approaches, combining MRI with PET [64], SPECT [70,71], or fluorescence imaging [72,75], which compensates for the limitations of each method individually.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [75]
In animal models, reduction in amyloid plaque burden, decrease in neuroinflammation and oxidative stress, and improvement in cognitive functions in behavioral tests have been demonstrated.
“In animal models, a reduction in the burden of amyloid plaques [58,68,75], a decrease in neuroinflammation and oxidative stress, as well as an improvement in cognitive functions in behavioral tests [58,64,72,73,83,85] have been demonstrated.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [75]
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- Authors
- Zhang, L., Lin, J., Xiang, K., Shi, T., & Guo, B.
- Affiliations
- Wannan Medical College (CN)
- Nanjing Drum Tower Hospital (CN)
- Corresponding author
- Zhang, Lei
- Shi, Tianshu
- Guo, Baosheng
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 376
- Pages
- 470-487
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4403662929
- Cited by
- 26
- References
- 120
- Citations by year
- 2026: 16 · 2025: 10
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- Alzheimer's disease, engineered exosomes, activated neutrophils, mitochondrial function, amyloid-beta toxicity, curcumin, superparamagnetic iron oxide nanoparticles, MMP-2, targeted drug delivery, early diagnosis, neuroprotection, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Brain, Curcumin, Humans, Male, Mice, Inbred C57BL, Mitochondria, Neurons, Neutrophils, Amyloid beta-Peptides, Matrix Metalloproteinase 2, Mice, Exosomes
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