期刊
NANO LETTERS
卷 19, 期 10, 页码 7334-7341出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b02958
关键词
Framework nucleic acid; ischemic stroke; positron emission tomography; complement component Sa; intrathecal injection
类别
资金
- University of Wisconsin-Madison
- National Institutes of Health [P30CA014520]
- National Natural Science Foundation of China [81760417, 81660230, 81871031]
- Science and Technology Program of Jiangxi, China [2016ACB21019, 2018ACB20020]
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.
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