Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus

Byungji Kim, Hong Bo Pang, Jinyoung Kang, Ji Ho Park, Erkki Ruoslahti, Michael J. Sailor

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish (US)
Article number1969
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Bibliographical note

Funding Information:
This work supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement HR0011-13-2-0017, in part by grant CA152327 from the National Cancer Institute of the U.S. National Institutes of Health (E.R.), and by grant EB022652 from National Institute of Biomedical Imaging and Bioengineering (H.P.). The content of the information within this document does not necessarily reflect the position or the policy of the Government. Furthermore, this project has been funded in part by the National Institutes of Health, through contract number R01 AI132413-01

Funding Information:
This work supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement HR0011-13-2-0017, in part by grant CA152327 from the National Cancer Institute of the U.S. National Institutes of Health (E.R.), and by grant EB022652 from National Institute of Biomedical Imaging and Bioengineering (H.P.). The content of the information within this document does not necessarily reflect the position or the policy of the Government. Furthermore, this project has been funded in part by the National Institutes of Health, through contract number R01 AI132413-01.

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