Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus

Nature Communications
Byungji KimMichael J Sailor

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.

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Citations

Aug 10, 2019·Lab on a Chip·Ruhollah Habibi, Adrian Neild
Oct 1, 2019·Advanced Materials·Byungji KimMichael J Sailor
Nov 21, 2019·Nanoscale·Tang TangHong-Bo Pang
Mar 4, 2020·Nanoscale·Pingsai LungQuan Li
Mar 4, 2020·Expert Opinion on Biological Therapy·Vivian Weiwen XueWilliam Chi Shing Cho
Oct 5, 2019·Nature Communications·Brendan P DyettCharlotte E Conn
Jun 30, 2019·Advanced Materials·C Wyatt ShieldsSamir Mitragotri
Jul 30, 2020·Nanomaterials·Marina Martínez-Carmona, María Vallet-Regí
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Apr 17, 2020·Angewandte Chemie·Shuangqian YanXiaogang Liu
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Oct 28, 2019·Nature Reviews. Materials·Yuanwen Jiang, Bozhi Tian
Dec 15, 2020·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Puneet Tyagi
Feb 19, 2021·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Byungji KimMichael J Sailor
Mar 19, 2021·ACS Infectious Diseases·Carly DeusenberyAnita Shukla
Mar 16, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tang TangHong-Bo Pang
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Jun 30, 2019·ACS Applied Materials & Interfaces·Terence TieuNicolas H Voelcker
Jul 10, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Cassidy C DolstraDarryl Y Sasaki

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Methods Mentioned

BETA
Confocal
PCR
transfection
fluorescence-activated cell sorting
flow cytometry
confocal microscopy
FACS

Software Mentioned

FlowJo
ImageJ

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