Oxidative stress due to Cu 2+ -triggered aggregation of β-amyloid protein (Aβ) and reactive oxygen species (ROS) overexpression in the brain is an important hallmark of early stages of Alzheimer's disease (AD) pathogenesis. The ideal modulator for improving the oxidative stress microenvironment in AD brains should take both Cu 2+ and ROS into consideration, which has been rarely reported. Here, a combined therapeutic strategy was achieved by co-encapsulating superoxide dismutase (SOD) and catalase (CAT) in imine-linked covalent organic frameworks (COFs), which were modified with peptide KLVFF (T5). The nanocomposite SC@COF-T5 exhibited an oxidative stress eradicating ability through ROS elimination and Cu 2+ chelation, combined with the inhibition of Aβ42 monomer aggregation and disaggregation of Aβ42 fibrils. In vivo experiments indicated that SC@COF-T5 with a high blood-brain barrier (BBB) penetration efficiency was effective to reduce Aβ deposition, expression of pro-inflammatory cytokines, ROS levels, and neurologic damage in AD model mice, consequently rescuing memory deficits of AD mice. This work not only confirms the feasibility and merits of the therapeutic strategy regarding multiple targets for treatment of early AD pathogenesis but also opens up a novel direction for imine-linked COFs in biomedical applications.
Keyphrases
- oxidative stress
- reactive oxygen species
- dna damage
- blood brain barrier
- cell death
- diabetic rats
- ischemia reperfusion injury
- induced apoptosis
- cerebral ischemia
- cognitive decline
- cell proliferation
- stem cells
- aqueous solution
- traumatic brain injury
- poor prognosis
- transcription factor
- high fat diet induced
- metal organic framework
- binding protein
- type diabetes
- small molecule
- skeletal muscle
- working memory
- multiple sclerosis
- white matter
- heat shock
- protein protein
- amyotrophic lateral sclerosis
- long non coding rna
- smoking cessation