Nanostructured Microparticles Repolarize Macrophages and Induce Cell Death in an In Vitro Model of Tumour-Associated Macrophages

Macrophages (M & phi;s) in their pro-inflammatory state (M1) suppress tumour growth, while tumour-associated M & phi;s (TAMs) can promote tumour progression. The aim of this study was to test the hypothesis that targeted delivery of the immune activator poly(I:C) in aspherical silica microrods (& mu;Rs) can repolarize TAMs into M1-like cells. & mu;Rs (10 & mu;m x 3 & mu;m) were manufactured from silica nanoparticles and stabilized with dextran sulphate and polyethyleneimine. The THP-1 cell line, differentiated into M & phi;s, and primary human monocyte-derived M & phi;s (HMDMs) were treated with tumour-cell-conditioned medium (A549), but only HMDMs could be polarized towards TAMs. Flow cytometry and microscopy revealed elevated uptake of & mu;Rs by TAMs compared to non-polarized HMDMs. Flow cytometry and qPCR studies on polarization markers showed desirable effects of poly(I:C)-loaded MPs towards an M1 polarization. However, unloaded & mu;Rs also showed distinct actions, which were not induced by bacterial contaminations. Reporter cell assays showed that & mu;Rs induce the secretion of the inflammatory cytokine IL-1 & beta;. Macrophages from Nlrp3 knockout mice showed that & mu;Rs in concentrations as low as 0.5 & mu;R per cell can activate the inflammasome and induce cell death. In conclusion, our data show that & mu;Rs, even if unloaded, can induce inflammasome activation and cell death in low concentrations.