Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells

Peptide–Gold Nanoparticle Hybrids as Promising Anti‐Inflammatory Nanotherapeutics for Acute Lung Injury: In Vivo Efficacy, Biodistribution, and Clearance

“…It has been confirmed that this fluorescence labeling does not alter the bioactivity of both P12 and P13. [16b] Using these fluorescent nanoparticles with multi‐parameter flow cytometry analysis, we were able to identify the subpopulations of the BAL cells, including macrophages (CD11b + F4/80 + ), neutrophils (CD11b + Gr1 + ), monocytes (CD11b + Gr1 low ), dendritic cells (DCs) (CD11c + Gr1 low ), B cells (CD19 + ), and T cells (CD3 + ) (Figure b), and quantify the internalized nanoparticles in each subtype of the BAL cells by measuring the Cy5 fluorescence intensity comparing to the baseline.…”

“…Through high‐throughput screening, we identified a group of hybrids that were capable of inhibiting multiple TLR pathways in human mononuclear immune cells (including macrophages) in vitro . Among them, the lead nanoparticle hybrid (designated P12) showed potent inhibitory activity on the signaling of TLRs 2, 3, 4 and 5, as well as the downstream proinflammatory cytokine production . One mechanism of action of the inhibitory activity of P12 was through blocking the endosomal acidification after cellular internalization.…”

“…One mechanism of action of the inhibitory activity of P12 was through blocking the endosomal acidification after cellular internalization. [16b] Based on these promising characteristics, we hypothesized that P12 is capable of alleviating excessive inflammation in ALI/ARDS and holds great potential for clinical translation.…”

Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics

“…One exciting invention is the development of a completely novel peptide-GNP hybrid system as a next generation nano-inhibitor led by Yang et al (2015, 2016). The system is made of a GNP core coated with a hexapeptide layer to enhance the physiological stability of the GNP, change the surface physicochemical characteristics, and enable the biological activity (Yang et al, 2011, 2013).…”

“…Further studies conferred the anti-inflammatory activity of P12 in correcting LPS-induced gene expressions, reducing the subsequent pro-inflammatory cytokine production (IL-12p40, MCP-1, and IFN-γ), and increasing the anti-inflammatory cytokine IL-1RA. In searching for the mechanism of action, delicate experiments were performed to show that the potent inhibitory activity of P12 is mainly due to its endosomal pH modulation capability (Yang et al, 2016). Like chloroquine (CQ), a lysotropic agent that can elevate endosome/lysosome pH, P12 was able to prevent the endosomal acidification process, which in turn attenuated downstream signal transduction of endosomal-dependent TLR signaling.…”