<P>Except for the few exceptions where topical administration is feasible, progress towards broad clinical application of nucleic acid therapeutics requires development of effective systemic delivery strategies. The central nervous system repres...
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https://www.riss.kr/link?id=A107638973
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2013
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SCI,SCIE,SCOPUS
학술저널
866-873(8쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P>Except for the few exceptions where topical administration is feasible, progress towards broad clinical application of nucleic acid therapeutics requires development of effective systemic delivery strategies. The central nervous system repres...
<P>Except for the few exceptions where topical administration is feasible, progress towards broad clinical application of nucleic acid therapeutics requires development of effective systemic delivery strategies. The central nervous system represents a particularly difficult organ for systemic delivery due to the blood-brain barrier. We previously reported a nanoparticulate delivery system for targeted brain delivery of oligonucleotides upon systemic administration, i.e. liposome-encapsulated polyethylenimine/oligonucleotides polyplexes. In this study, cellular uptake and intracellular trafficking of the nanoparticles were further investigated using <I>in situ</I> brain perfusion technique followed by colocalization and fluorescence resonance energy transfer techniques. The brain endothelial uptake and possibly parenchymal accumulation were readily visualized upon administration via internal carotid artery perfusion. The nanoparticles were colocalized with early-endosome antigen, which confirms the brain endothelial uptake through transferrin receptor-mediated endocytosis. Fluorescence resonance energy transfer analysis also suggested the nanoparticles entered the brain endothelial cells while maintaining their integrity. Together, the enhanced brain uptake, as claimed previously, of the antibody-targeted nanoparticles was clearly confirmed with more convincing evidences. In addition, the experimental techniques described here should be applicable to the studies involving nanoparticle-mediated brain delivery of nucleic acid therapeutics.</P>