In this study, we explained in detail a targeted nano-photo-thermal therapy (NPTT) method to induce selective apoptosis in cancer cells. Folate-conjugated gold nanoparticles (F-AuNPs) were synthesized by tailoring the surface of AuNPs with folic acid to enhance the specificity of NPTT. KB cancer cells, as a folate receptor over-expressing cell line, and L929 normal cells with low level of folate receptors were incubated with the synthesized F-AuNPs and then irradiated with various laser intensities and exposure durations. Following various regimes of NPTT, we assessed the level of cell viability and the ratio of apoptosis/necrosis. No significant cytotoxicity was observed for both cell lines at concentrations up to 40 μM of F-AuNPs. Moreover, no significant cell lethality occurred for various laser irradiation conditions. The viability of KB and L929 cells incubated with F-AuNPs (40 μM; 6 h) and then irradiated by laser (1 W/cm; 2 min) was 57 and 83%, respectively. It was also demonstrated that the majority of cancer cell death is related to apoptosis (41% apoptosis of 43% overall cell death). In this process of F-AuNPs based NPTT, it may be concluded that the main factor determining whether a cell dies due to apoptosis or necrosis depends on laser irradiation conditions. In this study, we explained in detail a targeted nano-photo-thermal therapy (NPTT) method to induce selective apoptosis in cancer cells.

Background: Despite considerable advances in nano-photo-thermal therapy (NPTT), there have been a few studies reporting in-depth kinetics of cell death triggered by such a new modality of cancer treatment. Objective: In this study, we aimed to (1) investigate the cell death pathways regulating the apoptotic responses to NPTT; and (2) ascertain the effect of NPTT on cell cycle progression. Methods: Folate conjugated gold nanoparticle (F-AuNP) was firstly synthesized, characterized and then assessed to determine its potentials in targeted NPTT. The experiments were conducted on KB nasopharyngeal cancer cells overexpressing folate receptors (FRs), as the model, and L929 normal fibroblast cells with a low level of FRs, as the control. Cytotoxicity was evaluated by MTT assay and the cell death mode (i.e., necrosis or apoptosis) was determined through AnnexinV/FITC-propidium iodide staining. Next, the gene expression profiles of some key apoptotic factors involved in the mitochondrial signaling pathway were investigated using RT-qPCR. Finally, cell cycle phase distribution was investigated at different time points post NPTT using flow cytometric analysis. Results: The obtained results showed that KB cell death following targeted NPTT was greater than that observed for L929 cells. The majority of KB cell death following NPTT was related to apoptosis. RT-qPCR analysis indicated that the elevated expression of Bax along with the depressed expression of Bcl-xL, Survivin and XIAP may involve in the regulation of apoptosis in response to NPTT. Flow cytometric analysis manifested that 16-24 hours after NPTT, the major proportion of KB cells was in the most radiosensitive phases of the cell cycle (G2/M). Conclusion: This study extended the understanding of the signaling pathway involved in the apoptotic response to NPTT. Moreover, the potential effect of NPTT on sensitizing cancer cells to subsequent radiation therapy was highlighted.

Cabazitaxel is a second-generation semisynthetic taxane. The recognized anti-neoplastic effect of Cabazitaxel is cell cycle perturbation by inducing arrest at G2/M. Since glioblastoma tumors have a relatively high expression of P-gp, it is encouraging to find a treatment that is effective against these tumors. This study was conducted to examine the radiosensitizing potential of Cabazitaxel against U87MG cells. In order to evaluate the effect of Cabazitaxel, cells were treated with different concentrations of the drug at different time intervals and then cytotoxicity and cell cycle were assessed using MTT and flow cytometry assays, respectively. Annexin/PI and real-time polymerase chain reaction (PCR) assays were used to evaluate the extent of apoptosis. Cabazitaxel exerted a consistent G2/M arrest and resulted in a concentration- and time-dependent toxicity. Cabazitaxel enhanced the cytotoxicity response of U87MG cells to radiation. Apoptosis increased following Cabazitaxel-IR administration. At the same time, these results were further supported by apoptotic genes regulation. This study provides the first preclinical evidence supporting that Cabazitaxel can render U87MG cells more susceptible to the cytotoxicity of radiation and could potentially be administered in combination modalities as a promising cell cycle-specific radiosensitizer for the future steps of in vivo evaluation.