An increase in mouse tumor growth by an<i>in vivo</i>immunomodulating effect of titanium dioxide nanoparticles

Abstract

Here, we investigated whether titanium dioxide (TiO₂) nanoparticles affect in vivo tumor growth through the modulation of mononuclear leukocytes. In vitro lymphocyte proliferation by lipopolysaccharide (LPS) or concanavalin A (ConA) was reduced by < 25 nm TiO₂ with a dose-dependent manner. Similarly, TiO₂ nanoparticles inhibited nitric oxide (NO) production from bone marrow-derived macrophages obtained from naïve mice. When mice were intraperitoneally (IP) injected with < 25 or < 100 nm TiO₂ once a day for 7 days, total cell number of splenocytes was reduced in the spleen of TiO₂ nanoparticle-exposed mice. Both CD4+ and CD8+ T-lymphocyte numbers were significantly decreased and B-lymphocyte development was retarded by host exposure to the TiO₂ nanoparticles. LPS-stimulated spleen cell proliferation was significantly reduced by host exposure to < 25 or < 100 nm TiO₂, but no changes were detected in ConA-stimulated spleen cell proliferation. Further, LPS-stimulated cytokine production by peritoneal macrophages and the percentage of NK1.1+ natural killer cells among splenocytes was reduced by the host exposures to the TiO₂ nanoparticles. When mice were IP injected with TiO₂ nanoparticles once a day for 28 days prior to the subcutaneous implantation of B16F10 melanoma cells, tumor growth was subsequently significantly increased. Collectively, these results show that TiO₂ nanoparticles may damage the development and proliferation of B- and T-lymphocytes, reduce the activity of macrophages, and decrease natural killer (NK) cell population levels, outcomes that appear to lead to an increase in tumor growth in situ. These studies allow us to suggest that TiO₂ nanoparticles might have the potential to enhance tumor growth through immunomodulation of B- and T-lymphocytes, macrophages, and NK cells.