Interaction between Macrophages and Nanoparticles: In Vitro 3D Cultures for the Realistic Assessment of Inflammatory Activation and Modulation of Innate Memory

Understanding the modes of interaction between human monocytes/macrophages and engineered nanoparticles is the basis for assessing particle safety, in terms of activation of innate/inflammatory reactions, and their possible exploitation for medical applications. In vitro assessment of nanoparticle-macrophage interaction allows for examining the response of primary human cells, but the conventional 2D cultures do not reproduce the three-dimensional spacing of a tissue and the interaction of macrophages with the extracellular tissue matrix, conditions that shape macrophage recognition capacity and reactivity. Here, we have compared traditional 2D cultures with cultures on a 3D collagen matrix for evaluating the capacity gold nanoparticles to induce monocyte activation and subsequent innate memory in human blood monocytes in comparison to bacterial LPS. Results show that monocytes react to stimuli almost in the same way in 2D and 3D cultures in terms of production of TNF alpha and IL-6, but that notable differences are found when IL-8 and IL-1Ra are examined, in particular in the recall/memory response of primed cells to a second stimulation, with the 3D cultures showing cell activation and memory effects of nanoparticles better. In addition, the response variations in monocytes/macrophages from different donors point towards a personalized assessment of the nanoparticle effects on macrophage activation.