Figure 1. Fusogenic porous silicon nanoparticles directly deliver siIRF5 into the cell cytoplasm of macrophages.

(a) Schematic depicting the peptide-targeted, fusogenic porous silicon nanoparticles (F-pSiNPs) and their mode of action in delivering and silencing the Irf5 gene in macrophages, as a broad-class strategy for treatment of Gram-positive (Methicilin-resistant Staphylococcus aureus, MRSA) and Gram-negative (Pseudomonas aeruginosa) bacterial infections. (b) Representative confocal microscope image of J774a.1 macrophage cells treated with fusogenic porous silicon nanoparticles (F-pSiNPs). Left image: cells were treated with fusogenic pSiNPs wherein the lipid coating on the pSiNPs contained the lipophilic DiI membrane dye (red channel). The pSiNP core carried a non-labeled, non-functional siRNA payload. Lysosomes are stained with LysoTracker Green (LysoG, green channel) and cell nucleus is stained with DAPI (blue channel). Right image: cells were treated with F-pSiNPs wherein the lipid coating contained the lipophilic DiO membrane dye (green channel). The pSiNP core carried a Cy3-labeled siRNA payload (red channel) and the cell nucleus is stained with DAPI (blue channel); (c) confocal microscope image of J774a.1 macrophage cells equivalent to (b) but using non-fusogenic porous silicon nanoparticles (NF-pSiNPs). Left image: DiI membrane stain loaded in the lipid coating of the pSiNPs (red); lysosomes stained with LysoTracker Green (green channel); DAPI nuclear stain (blue channel). Right image: DiO membrane stain loaded in the lipid coating of the pSiNPs (green channel); Cy3-siRNA loaded in the pSiNP core (red channel); DAPI nuclear stain (blue channel). Nanoparticles in (b) and (c) contained CRV targeting peptides pendant to the lipid coating of the pSiNPs.