Kinetics of cell death triggered photothermally using folate-conjugated gold nanoparticles and various laser irradiation conditions in cancer cells

Introduction: In this study, we explore in detail cell-specific targeting efficacy of nano-photo-thermal therapy (NPTT) method and the resulting responses that are induced by variable laser intensities and exposure times in cancer cells to induce selective apoptosis. We delineate the synthesis of a high-yielding synthetic F-AuNPs by tailoring the surface of gold nanoparticles with folic acid to enhance cell selectivity and specificity. Materials and Methods: For this purpose, synthesized F-AuNPs treated cells were irradiated with various laser intensities and exposure duration. Both KB cancer cells, as a folate receptor over-expressing cell line, and L929 normal cells, with low level of folate receptors were used. Following various regimes of NPTT, Cytotoxicity was assessed by MTT assay and comparison of induced apoptosis and necrosis in population of cells were depicted by Annexin/PI staining. Results: We report no significant cytotoxicity difference between KB and L929 cell lines at concentrations up to 40 μM of F-AuNPs. Moreover, no significant cell lethality occurred for various laser irradiation conditions. However, in photothermal therapy, the viability of KB and L929 cells was 57% and 83%, respectively. Flow cytometry clearly revealed the kinetics of cell death. The majority of cancer cell death was related to apoptosis (41% apoptosis of 43% overall cell death). Conclusion: Together, these findings confirm that F-AuNPs based NPTT can either induces cell death via apoptosis or necrosis. The main factor determining whether a cell will die due to apoptosis or necrosis on-demand with PTT depends on laser heating level. Our main target must be to only trigger apoptosis during PTT by using suitable irradiation conditions. As a result, folate targeting ability of the F-AuNPs and laser energy threshold to induce selective apoptosis in cancer cells were shown.