Titanium dioxide nanoparticle stimulating pro-inflammatory responses in vitro and in vivo for inhibited cancer metastasis

The interaction of engineered nanoparticles (NPs) with the immune system and the possibility of inflammation induction are of particularly interest. Titanium dioxide nanoparticles (TiO₂ NPs) are one of the most popular manufactured nanomaterials. In this study, we focused on the immune-modulatory effect of commercial P-25 TiO₂ NPs in vivo and in vitro and their crucial role in cancer metastasis.

The female C57BL/6 mice were injected into abdominal cavity with PBS or P-25 TiO₂ to investigate the immune-modulatory function of P-25. And breast cancer cells were intravenously (i.v.) injected into mouse to establish the liver and lung cancer metastasis model. Peritoneal macrophage was used to investigate the macrophage polarization in vitro.

Results showed us that peritoneal macrophage exposed to P-25 TiO₂ NPs displayed activated M1 macrophage response, as evidenced by the increased mRNA expression of interleukin-1β (IL1β), IL6, TNFα, CCR7 and inducible nitric oxide synthase (iNOS). After exposure of TiO₂ NPs in vivo for 21 days, the body weights of mice decreased significantly, which were accompanied by an infiltration of immune cells in liver and spleen in 20 mg/kg BW treated group. Importantly, the production of pro-inflammatory cytokines in liver, spleen and the serum were amplified, which indicated the tissue and systemic inflammation induced by TiO₂ NPs. In addition, the activation of immune response induced by P-25 TiO₂ NPs was correlated with their ability to inhibit cancer metastasis.

Our results delineated the stimulating pro-inflammatory response induced by P-25 TiO₂ NPs and their outcome in vivo for cancer metastasis.