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Nat Commun. 2018 May 17;9(1):1969. doi: 10.1038/s41467-018-04390-7.

Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus.

Author information

1
Materials Science and Engineering Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA.
2
Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, 92037, USA.
3
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
4
Department of Nanoengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA.
5
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
6
Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, California, 93106-9610, USA.
7
Materials Science and Engineering Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA. msailor@ucsd.edu.
8
Department of Nanoengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA. msailor@ucsd.edu.
9
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA. msailor@ucsd.edu.

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.

PMID:
29773788
PMCID:
PMC5958120
DOI:
10.1038/s41467-018-04390-7
[Indexed for MEDLINE]
Free PMC Article

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