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

Abstract

BackgroundThe 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. MethodsIn 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. ResultsThe 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 μm 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 IC50 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. ConclusionsThese findings suggest that the newly synthesized composite may play a pivotal role in cancer treatment and are encouraging for future in vivo investigations.