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Brain-targeting delivery for RNAi neuroprotection against cerebral ischemia reperfusion injury.

Authors: An, S  Kuang, Y  Shen, T  Li, J  Ma, H  Guo, Y  He, X  Jiang, C 
Citation: An S, etal., Biomaterials. 2013 Nov;34(35):8949-59. doi: 10.1016/j.biomaterials.2013.07.060. Epub 2013 Aug 19.
Pubmed: (View Article at PubMed) PMID:23968852
DOI: Full-text: DOI:10.1016/j.biomaterials.2013.07.060

Nanoparticles (NPs) with modification of brain-targeting molecules have been extensively exploited for therapeutic gene delivery across the blood-brain barrier (BBB). As one of the effective RNA interference (RNAi) approaches, short hairpin RNA (shRNA) has been proved to be promising in the field of gene therapy. Apoptosis signal-regulating kinase 1 (Ask1) has been reported to be an important target for gene therapy against cerebral ischemia reperfusion injury. In this study, dendrigraft poly-l-lysine (DGL) was decorated by dermorphin (a mu-opiate receptor agonist) through PEG for efficient brain-targeting, then complexed with anti-Ask1 shRNA plasmid DNA, yielding the DGL-PEG-dermorphin/shRNA NPs. The DGL-PEG-dermorphin/shRNA NPs were characterized and estimated the brain-targeting ability. In vitro, increased cellular uptake and transfection efficiency were explored; in vivo, preferable accumulation and gene transfection in brain were showed in images. The DGL-PEG-dermorphin/shRNA NPs also revealed high efficiency of neuroprotection. As a result of RNAi, corresponding mRNA was distinctly degraded, expression of Ask1 protein was obviously suppressed, apoptotic cell death was apparently decreased and cerebral infarct area was significantly reduced. Above all, DGL-PEG-dermorphin/shRNA NPs were proved to be efficient and safe for brain-targeting RNAi neuroprotection against cerebral ischemia reperfusion injury.

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CRRD Object Information
CRRD ID: 10412642
Created: 2015-11-18
Species: All species
Last Modified: 2015-11-18
Status: ACTIVE



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