Enhanced Anti-inflammatory Activity of Peptide–Gold Nanoparticle Hybrids upon Cigarette Smoke Extract Modification through TLR Inhibition and Autophagy Induction

• DOI: 10.1021/acsami.9b10536
• Publication Date: 2019-08-14T20:27:37Z
• Authors: Wei Gao; Lu Wang; Kun Wang; Liya Sun; Yafei Rao; Aying Ma; Min Zhang; Qiang Li; Hong Yang
• Keywords: Inflammation; Male; 0303 health sciences; NF-E2-Related Factor 2; THP-1 Cells; Acute Lung Injury; Smoking; Anti-Inflammatory Agents; Metal Nanoparticles; 3. Good health; Mice, Inbred C57BL; Toll-Like Receptor 4; 03 medical and health sciences; Autophagy; Animals; Humans; Gold; Peptides; Heme Oxygenase-1

Overwhelming uncontrolled inflammation is the hallmark of pathophysiological features many acute and chronic inflammatory diseases, such as sepsis allergy autoimmune disorders. It important to develop potent pharmacological interventions effectively control detrimental reactions in these diseases. Recently, we have developed a special class peptide-gold nanoparticle hybrid system that can inhibit Toll-like receptor 4 (TLR4) signal transduction pathways decrease its downstream responses. Herein, serendipitously discovered tiny amount cigarette smoke extract (CSE, 1%) was able significantly enhance inhibitory activity hybrids on TLR4-mediated Mechanistically, it found active components CSE were adsorb onto largely increased their cellular uptake THP-1 cell-derived macrophages. Such high not only enhanced inhibition endosomal acidification required for TLR4 activation but also contributed autophagy induction subsequent antioxidant protein expression. Consequently, this duel action strengthened anti-inflammatory cells an lung injury (ALI) mouse model. This work aids our fundamental understanding nanoparticles regulating innate immune provides new way design nanotherapeutics diseases ALI.