Nanoparticle-induced inflammation can increase tumor malignancy.

Nanomaterials, such as aluminum oxide, have been regarded with high biomedical promise as potential immune adjuvants in favor of their bulk counterparts. For pathophysiological conditions where elevated immune activity already occurs, the contribution of nanoparticle-activated immune reactions remains unclear. Here, we investigated the effect of spherical and wire-shaped aluminum oxide nanoparticles on primary splenocytes and observed a clear pro-inflammatory effect of both nanoparticles, mainly for the high aspect ratio nanowires. The nanoparticles resulted in a clear activation of NLRP3 inflammasome, and also secreted transforming growth factor β. When cancer cells were exposed to these cytokines, this resulted in an increased level of epithelial-to-mesenchymal-transition, a hallmark for cancer metastasis, which did not occur when the cancer cells were directly exposed to the nanoparticles themselves. Using a syngeneic tumor model, the level of inflammation and degree of lung metastasis were significantly increased when the animals were exposed to the nanoparticles, particularly for the nanowires. This effect could be abrogated by treating the animals with inflammatory inhibitors. Collectively, these data indicate that the interaction of nanoparticles with immune cells can have secondary effects that may aggravate pathophysiological conditions, such as cancer malignancy, and conditions must be carefully selected to finely tune the induced aspecific inflammation into cancer-specific antitumor immunity. STATEMENT OF SIGNIFICANCE: Many different types of nanoparticles have been shown to possess immunomodulatory properties, depending on their physicochemical parameters. This can potentially be harnessed as a possible antitumor therapy. However, in the current work we show that inflammation elicited by nanomaterials can have grave effects in pathophysiological conditions, where non-specific inflammation was found to increase cancer cell mobility and tumor malignancy. These data show that immunomodulatory properties of nanomaterials must be carefully controlled to avoid any undesired side-effects.