Synthesis and stabilization of anatase form of biomimetic TiO2 nanoparticles for enhancing anti-tumor potential

Abstract

The present study emphasizes the stabilization of the biologically active anatase form of titanium dioxide (TiO2) nanoparticles (NP). TiO2 NP require stringent conditions for chemical synthesis and are usually a mixture of biologically inactive bulk rutile and the active bulk anatase forms. We utilized the culture pellet of the Exiguobacterium aestuarii SBG4 MH185868 to synthesize and stabilize the anatase form of TiO2 NP. The NP showed λ max at ∼350 nm and scanning electron microscope micrographs indicated their oval and spherical shape. Steric stabilized anatase TiO2 NP exhibited substantial cytotoxicity of up to 80% reduction in cell viability at 100 µg against cervical cancer derived HeLa and SiHa cell lines, whereas the rutile form showed least cytotoxicity. Clonogenic inhibition assay of HeLa cells showed dose-dependent decline with a 75% reduction in colony formation at 100 µg TiO2 NP and cell migration assay revealed significant inhibition in recovery of the wound/scratch in presence of anatase form of TiO2 NP (10–33% at 24 h and 42–79% at 48 h). Co-incubation of HeLa cells with anatase TiO2 NP in chorioallantoic membrane of embryonated chick eggs prevented the formation of new capillaries (20 ± 5% compared with control groups), indicating appreciable anti-angiogenic activity of the NP. Further, TiO2 NP tagged with doxorubicin and paclitaxel exhibited enhanced cytotoxicity against cancer cells at very low concentrations of 9 and 120 nM itself, indicating their anti-tumor potential. In conclusion, biomimetic anatase TiO2 NP have significant anti-proliferative and anti-angiogenic activity and can have potential application in tagging with generic anti-cancer drugs for enhanced cytotoxicity against cancer cells.

Keywords

• titanium dioxide
• nanoparticles
• clonogenicity
• cell migration
• anti-angiogenic activity