The potential of HSA-stabilized zinc oxide nanoparticles as radiosensitizers to enhance the cytotoxic effects and radiosensitivity of cervical cancer cells

Abstract

Abstract Background Cervical cancer is a significant cause of death among women worldwide, and limited treatment approaches are available for patients with metastatic or recurrent disease. Recently, the combination of nanoparticles (NPs) and radiotherapy (RT) has been shown to be an effective treatment because it enhances the sensitivity of cancer cells to radiation. ZnO NPs stabilized with HSA have become one of the most popular types of metal oxide nanoparticles because of their cost-effectiveness and minimal toxicity. Therefore, our study aimed to investigate the radiosensitization effects of HSA/ZnO-NPs on cervical (HeLa) cancer cells under megavoltage (MV) X-ray irradiation. Methods HSA/ZnO-NPs were prepared and characterized by SEM and Dynamic Light Scattering (DLS) technique. The cytotoxicity of HSA/ZnO NPs was evaluated in HeLa cells via an MTT assay. The radiosensitization effects were investigated under megavoltage X-ray irradiation using a clonogenic survival assay and quantifying γH2AX foci. Moreover, apoptosis and cell cycle analyses were conducted using a Muse™ Cell Analyzer. Results HSA/ZnO-NPs reduced the viability of HeLa cells in a dose-dependent manner, which revealed that the IC50 of HSA/ZnO-NPs was approximately 30 µg/mL. The prepared particles exhibited moderate aggregation regarding hydrodynamic size (approximately 300–400 nm) and a negative zeta potential charge. Compared to the control group, combining HSA/ZnO-NPs with irradiation reduced the colony-forming ability and survival of HeLa cells by approximately 51% and 71% for 2 and 4 Gy, respectively. Correspondingly, the results of the apoptosis analysis showed that combining HSA/ZnO-NPs with irradiation significantly increased apoptosis induction by approximately 39.15% and 77.67% for 2 and 4 Gy, respectively. In addition, we observed a significant increase in cell cycle arrest at the S phase, by about 11.3% and 19.3% for 2 and 4 Gy, respectively. Conclusions HSA/ZnO-NPs could significantly enhance the cytotoxic effects of ionizing radiation, which suggests the promising potential of cervical cancer radiotherapy under megavoltage X-ray irradiation.

Keywords

• ZnO nanoparticles
• Cervical cancer cells
• Radiosensitizer
• Ionizing radiation
• Human serum albumin