Cancer Therapeutic Effects of Titanium Dioxide Nanoparticles Are Associated with Oxidative Stress and Cytokine Induction

Abstract

Nanoparticles (NPs) are considered to influence the inflammatory process; however, the precise mechanism and the significance in tumors are still not clear. In this study, when CT26 and LL2 mouse cancer cells were treated with 6-nm anatase titanium dioxide NPs (TDNPs) without ultraviolet irradiation, oxidative stress and induction of inflammatory cytokines were observed. Oxidative stress was further increased by disease-associated conditions such as high glucose concentrations and hypoxia. Inhaled or orally administered TDNPs generated granulomatous lesions in the lungs and colon of the rodent models tested, with increased oxidative stress and inflammatory cytokines. Oxidative stress and inflammatory cytokines were also found in cancer cells treated with gold or carbon black NPs. Treatment of CT26 cells with 10- to 70-nm rutile TDNPs showed that smaller NPs produced more oxidative stress and inflammatory cytokines than larger ones did. To avoid diffusion of TDNPs and to minimize toxicity, 10-nm TDNPs were suspended in a collagen gel inserted into a subcutaneous tumor in a CT26 mouse. A single TDNP treatment via this method inhibited tumor growth in a size- and dose-dependent manner, and resulted in lower levels of urinary 8-OHdG when compared to systemically administered TDNPs. These findings suggest that TDNPs might be useful for the local treatment of tumors.

Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

“…single-strand breaks (SSBs), double-stranded breaks (DSBs)) by direct or indirect effect. With X-ray irradiation, amplified production of ROS and secondary electron from the high-Z nanoparticle result in cytotoxic enhancement on cells (Reproduced with permission from reference: [144], copyright 2018 Elsevier B.V) that titanium dioxide NPs could induce higher levels of inflammatory cytokines production in lung and colon cancer models [75]. Furthermore, small airway epithelial cells exposed to gold NPs could induce protein expression in neighboring lung fibroblasts in co-culture systems.…”

Biological mechanisms of gold nanoparticle radiosensitization

“…NPs could also mediate bystander signalling, for example, small titanium dioxide NPs induce higher levels of oxidative stress and production of inflammatory cytokines. The expression of cytokine macrophage inflammatory protein-1 alpha (MIP-1α) and high-mobility group protein 1 (HMGB1) were found to be expressed in the presence of these NPs, both in vitro and in vivo (Fujiwara et al 2015 ). This may play a role in enhancing oxidative stress as HMGB1 is known to be an inflammatory macrophage-secreted cytokine, which is activated by TNFα (tumour necrosis factor alpha) and IL-1β (interleukin 1 beta) (Andersson et al 2000 ; Tang et al 2009 ).…”

Nitrogen-Doped Titanium Dioxide Nanoparticles Modified by an Electron Beam for Improving Human Breast Cancer Detection by Raman Spectroscopy: A Preliminary Study

“…Highly reactive hydroxyl acts as a powerful oxidant, resulting in oxidative DNA damage to both single- and double-stranded DNA [ 30 ]. Fujiwara et al found that the oxidative stress produced in response to administration of 6 nm anatase titanium dioxide nanoparticles (on mouse lung and colon cancer cells) was enhanced by high glucose concentrations, acidic pH, hypoxia, high temperature, and the presence of advanced glycation end products [ 32 ].…”