Aptamer-Conjugated Framework Nucleic Acids for the Repair of Cerebral Ischemia-Reperfusion Injury.
Shiyong LiDawei JiangZachary T RosenkransTodd E BarnhartEmily B EhlerdingDalong NiJonathan W EngleWeibo CaiPublished in: Nano letters (2019)
Effective therapy for protecting dying neurons against cerebral ischemia-reperfusion injury (IRI) represents a substantial challenge in the treatment of ischemic strokes. Oxidative stress coupled with excessive inflammation is the main culprit for brain IRI that results in neuronal damage and disability. Specifically, complement component 5a (C5a) exacerbates the vicious cycle between oxidative stress and inflammatory responses. Herein, we propose that a framework nucleic acid (FNA) conjugated with anti-C5a aptamers (aC5a) can selectively reduce C5a-mediated neurotoxicity and effectively alleviate oxidative stress in the brain. Intrathecal injection of the aC5a-conjugated FNA (aC5a-FNA) was applied for the treatment of rats with ischemic strokes. Positron emission tomography (PET) imaging was performed to investigate the accumulation of aC5a-FNA in the penumbra and its therapeutic efficacy. Results demonstrated that aC5a-FNA could rapidly penetrate different brain regions after brain IRI. Furthermore, aC5a-FNA effectively protected neurons from brain IRI, as verified by serum tests, tissue staining, biomarker detection, and functional assessment. The protective effect of aC5a-FNA against cerebral IRI in living animals may pave the way for the translation of FNA from bench to bedside and broaden the horizon of FNA in the field of biomedicine.
Keyphrases
- oxidative stress
- ischemia reperfusion injury
- fine needle aspiration
- cerebral ischemia
- ultrasound guided
- resting state
- positron emission tomography
- pet imaging
- subarachnoid hemorrhage
- white matter
- nucleic acid
- computed tomography
- dna damage
- functional connectivity
- diabetic rats
- photodynamic therapy
- brain injury
- induced apoptosis
- blood brain barrier
- gold nanoparticles
- palliative care
- signaling pathway
- pet ct
- combination therapy
- label free
- physical activity
- sensitive detection
- real time pcr
- quantum dots
- loop mediated isothermal amplification