Title : Metal doped CuS nanoparticles as photothermal therapeutic approach against HeLa cancer cells
Abstract:
Background: Cancer is one of the most damaging diseases worldwide and has been responsible for millions of deaths. Conventional cancer therapies, including surgery, chemotherapy and radiotherapy, still have limitations, such as severe side effects and low efficiency. Nanomaterials are emerging therapeutic approaches for effective treatment of various cancers. These advanced nanomaterials absorb light so strongly and convert it efficiently into thermal energy. Therefore, new uses for nanomaterials in targeted cancer therapy are becoming known, and the efficacy of cancer photothermal therapy (PTT) technique has increased dramatically.
Objective: To investigate the anticancer effect of novel synthesized photothermal nanomaterials on the HeLa cancer cell line.
Methodology: A Copper sulfide (CuS) with metal ions doping nanoparticles were synthesized via wet chemical method. The structural properties of the nanoparticles were characterized using XRD techniques and TEM. The Optical properties of the synthesized nanoparticles were studied under UV-VIS and PL techniques. The temperature elevation of aqueous solutions of CuS and doped CuS nanoparticles as a function of exposure time was tested under light exposure. HeLa cancer cells were treated and irradiated with laser irradiation of 740 nm. MTT assay was used to investigate the effect of different synthesized nanoparticles on the viability of HeLa cell line. Induction of apoptosis was detected using the fluorescence microscope and flow cytometry. Autophagy was detected using acridine orange stain and flow cytometry. Results: All the synthesized nanoparticles show a covellite CuS phase structure where spherical shaped nanoparticles were formed. The particle size of the CuS is 14 nm, which is decreased by doping of iron and silver to less than 10 nm. Irradiation by a NIR laser beam at 740 nm resulted in an increase in the temperature of the CuS nanoparticle dispersed in an aqueous solution as a function of exposure time and nanoparticle concentration. The different used nanoparticles inhibited the growth of HeLa cells to various degrees, in a dose-dependent manner. The results show that there is no significant statistical inhibitory difference between the cells that were treated with the different nanoparticles and exposed to light and those that were not exposed to light. The most effective compound among the tested compounds after 48 h of treatment was Fe:CuS while the least effective was Ag:CuS. Fe:CuS induced apoptosis in HeLa cells after treatment for 48 h with an increase in the early apoptotic cells mean percentage from 4.7% to 28.6% as the concentration of Fe:CuS increased from 0 to 200 µg/mL, respectively. Treatment of HeLa cells with Fe:CuS for 48h caused a significant increase in the AVOs mean percentage from 4.9% to 33.7% as the concentration of Fe:CuS increased from 0 to 200 µM.
Conclusion: New synthesized nanoparticles showed different anti-inhibitory effects with Fe:CuS being the most effective. Fe:CuS induced apoptosis and autophagy in HeLa cells. Further studies are required to determine the cell death mechanism and the effect of autophagy on cell death.