Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus

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The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2018-05
Language
English
Article Type
Article
Citation

NATURE COMMUNICATIONS, v.9

ISSN
2041-1723
DOI
10.1038/s41467-018-04390-7
URI
http://hdl.handle.net/10203/242464
Appears in Collection
BiS-Journal Papers(저널논문)
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