Thallium and selenite doped carbonated hydroxyapatite: Microstructural features and anticancer activity assessment against human lung carcinoma

Background: The fabrication of nanostructure local delivery system from a biocompatible biomaterial is highly requested for biomedical applications. The therapeutic use of thallium was halted for its toxicity. We hypothesize that doping it on a biocompatible composite can work as a drug delivery system for its potential antineoplastic activity. Methods: In this study, a novel co-substitution containing Tl/Se ions within carbonated hydroxyapatite (CHAP) has been synthesized using a facial precipitation method at different concentrations of Tl ions. Results: The as-synthesized samples were investigated using XRD, which revealed a growth in a-axis rather than c-direction upon the elevation of Tl content. The topological investigations performed by SEM assured this growth trend and showed that the grain size was in the range of 1.4-3.5 mu m at x = 0.6. The surface charge measured by zeta potential illustrated that the highest negativity was - 15.95 mV and it was achieved at x = 0.6. The anticancer activity was assessed at the in vitro level by MTT assay against human non-small cell lung cancer cell line (A549) and human fibroblast-like fetal lung cell line (WI 38). The determined IC so values after 24 and 72 h of incubation showed a significantly more potent effect on the cancerous cell line compared to the normal one; 10 and 2 times, respectively at x = 0.6. Cell cycle and death mode analysis of treated cancerous cells by flow cytometry indicated a cell cycle arrest at G2/M phase and a prominent apoptotic activity. That was confirmed by the up-regulation of the pro-apoptotic genes; cytochrome c, caspase 3 and TP53 as measured by qRT-PCR. Conclusions: These findings suggest that the newly synthesized composite may play a pivotal role in cancer treatment and are encouraging for future in vivo investigations.