Issue 4, 2021

Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

Abstract

Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response (i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo, and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type.

Graphical abstract: Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

Supplementary files

Article information

Article type
Communication
Submitted
29 Oct 2020
Accepted
09 Feb 2021
First published
09 Feb 2021

Nanoscale Horiz., 2021,6, 330-340

Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

B. Kim, Q. Yang, L. W. Chan, S. N. Bhatia, E. Ruoslahti and M. J. Sailor, Nanoscale Horiz., 2021, 6, 330 DOI: 10.1039/D0NH00624F

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