Size-dependent cellular uptake and TLR4 attenuation by gold nanoparticles in lung adenocarcinoma cells.

To elucidate uptake mechanisms and immunomodulatory potential of differently sized gold nanoparticles (GNPs) in lung adenocarcinoma cells (A549) to enable their use as an adjunct therapy for treating inflammation-linked lung cancer. Internalization of the synthesized (5, 15 and 30 nm) GNPs by various endocytosis pathways was determined. Immunomodulatory mechanisms induced by differently sized GNPs in A549 cells in the presence of TLR4 and TLR9 ligands were evaluated. GNPs were size-dependently internalized efficiently by A549 cells. Various sized GNPs downregulated the expression of proinflammatory signaling molecules (5 nm most potent). Mechanistically, 5-nm GNPs attenuated TLR4 signaling by downregulating TLR4 expression in A549 cells. Our study suggests the use of immunomodulatory GNPs as an adjunct therapy against inflammation-linked lung cancer.