Enantioselective Modulation of Inflammatory Response through MAPK Pathway by Wavelike Chiral Nanoparticles

Infectious inflammation remains a major global health issue, so novel strategies to alleviate inflammatory responses are urgently required. Cinnabar (α-HgS) used in traditional Chinese medicine shows protective effects against inflammation, but low anti-inflammatory efficacies ascribed to poor solubility and bioavailability have hindered extensive applications of cinnabar. Nanoscale chirality provides chances to improve efficacies through enantiomer-dependent interactions between cells and chiral cinnabar nanoparticles (HgSNPs). Herein HgSNPs with intrinsically wavelike chirality were prepared through a one-pot seedless method, exhibiting efficacious alleviation of inflammation in vitro and in vivo by HgSNPs with laevorotatory chirality (l-HgSNPs) rather than those with dextrorotatory chirality (d-HgSNPs). The mitogen-activated protein kinase as a crucial pathway involved in inflammation and immunity was directly blocked by l-HgSNPs through inhibition of p38 phosphorylation, so the levels of pro-inflammatory cytokines were reduced significantly. This study showed an enantiomer-dependent immunological response to chiral HgSNPs, providing a novel protocol to efficaciously modulate health risks from infectious inflammation.