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S1B-5 Macrophage Gene Therapy in the Central Nervous System

神经药理学报 2018年第4期8卷 32-33页

作者： So Yoon Lee Cara Orji ZHANG Zi-jian ZHANG Hao-yun Anthony Bastian Adriana Galvez DOU Huan-yu Department of Biomedical Sciences Paul L.Foster School of Medicine Gradulate School of Biomedical Sciences Texas Tech University Health Sciences CenterEl PasoTexas79905USA Weifang Medical University ShandongChina

Regulation of immune responses is particular important in recovery after stroke,traumatic brain injury,and brain infections by inhibiting inflammation and reinstating rescue *** delivery based immunotherapy appears to have significant therapeutic potential for the treatment of neurological conditions by inhibition of neuroinflammation to prevent irreversible destructive ***,current gene delivery systems lack desired convenience,efficiency,and *** offers an attractive gene delivery system that overcome the immunogenic and long-term oncologic effects of the viral *** branched PEI lipids with PLGA,we developed a highly efficient core-shell nanoparticle(NP)gene delivery *** IL-4 plasmid DNA(pIL-4)loaded NPs(pIL-4-NPs)were effectively delivered pIL-4 to the human blood monocytes derived macrophages(MDM)and mouse bone marrow-derived macrophages(BMM).Furthermore,pIL-4-NPs quickly escaped lysosomes and entered the nuclei of these *** in vitro transfection assays,the pIL-4-NPs had higher transfection efficiency,in contrast,PEI25KPEI liposomes and PLGA NPs were unable to transfect MDM and *** lpsinduced inflammatory in vitro and in vivo models,transfection of pIL-4-NPs decreased lpsinduced pro-inflammatory cytokines,such as IL-1,IL6,and TNF-.Our findings indicate that pIL-4-NPs delivery system is capable of effectively deliver IL-4 plasmid DNA into human and murine macrophages,which consistently express IL-4 in vitro and in *** pIL-4-NPs dramatically diminished pro-inflammatory cytokines expression,exhibited antineuroinflammatory and neuroprotective efficacy when macrophages were activated by ***,branched PEI lipids and PLGA formed core-shell NPs are a promising gene delivery platform for immunotherapy in neurological ailments.

关键词： MDM In lpsinduced inflammatory

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