Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus

Byungji Kim, Hong-Bo Pang, Jinyoung Kang, Ji-Ho Park, Erkki Ruoslahti and Michael J. Sailor ()
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Byungji Kim: University of California, San Diego
Hong-Bo Pang: Sanford Burnham Prebys Medical Discovery Institute
Jinyoung Kang: University of California, San Diego
Ji-Ho Park: Korea Advanced Institute of Science and Technology (KAIST)
Erkki Ruoslahti: Sanford Burnham Prebys Medical Discovery Institute
Michael J. Sailor: University of California, San Diego

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-04390-7

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