Significance
We have developed a new class of nanoparticle-based inhibitors (i.e., peptide-GNP hybrids) targeting TLR4 signaling in macrophages. Through evidence-based engineering of the nanoparticle size, surface peptide ligand density and effective amino acid (phenylalanine, F) chain length, we identified a peptide-GNP hybrid, P12(G20), with enhanced anti-inflammatory activity. Specifically, P12(G20) was more potent in reducing inflammation in THP-1 cell-derived macrophages and in a LPS-induced ALI mouse model. More interestingly, P12(G20) facilitated long-term protection against lethal LPS challenge in vivo and induced endotoxin tolerance in vitro. We anticipate that these new hybrids would serve as the next generation anti-inflammatory nano-therapeutics for the treatment of ALI/ARDS or other acute and chronic inflammatory diseases.
Statement of significance
We have developed a new class of nanoparticle-based inhibitors (i.e., peptide-GNP hybrids) targeting TLR4 signaling in macrophages. Through evidence-based engineering of the nanoparticle size, surface peptide ligand density and effective amino acid (phenylalanine, F) chain length, we identified a peptide-GNP hybrid, P12(G20), with enhanced anti-inflammatory activity. Specifically, P12(G20) was more potent in reducing inflammation in THP-1 cell-derived macrophages and in a LPS-induced ALI mouse model. More interestingly, P12(G20) facilitated long-term protection against lethal LPS challenge in vivo and induced endotoxin tolerance in vitro. We anticipate that these new hybrids would serve as the next generation anti-inflammatory nano-therapeutics for the treatment of ALI/ARDS or other acute and chronic inflammatory diseases.