Nanoparticle-Mediated X-PDT: An Innovative Strategy to Enhance Radiation Therapy in Cervical Cancer Treatment
Nanoparticle-Mediated X-PDT: An Innovative Strategy to Enhance Radiation Therapy in Cervical Cancer Treatment
Mahsa Ejtema,1Nahid Chegeni,2,*
1. Department of Medical Physics, Faculty of Medicine, Ahvaz Jundishapur university of Medical Sciences, Ahvaz, Iran 2. Department of Medical Physics, Faculty of Medicine, Ahvaz Jundishapur university of Medical Sciences, Ahvaz, Iran
Introduction: Cervical cancer is a significant global health issue, necessitating the development of innovative treatment strategies. Photodynamic therapy (PDT) is an emerging approach in cancer treatment that utilizes light and photosensitizing agents to generate reactive oxygen species (ROS) for tumor destruction. However, traditional PDT has limitations in terms of tissue penetration depth and selectivity. To overcome these challenges, the concept of X-ray induced photodynamic therapy (X-PDT) has emerged in the field of nanomedicine. This novel approach involves the use of nanoparticles as radiosensitizers that can be activated by X-rays to produce ROS and enhance the therapeutic efficacy of radiation therapy. Among these nanoparticles, Copper-Cysteamine nanoparticles (Cu-Cy NPs) have demonstrated great potential as radiosensitizers. The unique mechanism of action of Cu-Cy NPs involves their ability to be activated by various forms of stimulations, including UV, X-ray, microwave, and ultrasound. Upon activation, these nanoparticles generate ROS, such as singlet oxygen and hydroxyl radicals, which induce oxidative stress and damage cancer cells. This dual activation mechanism of Cu-Cy NPs through X-rays and other forms of radiation makes them an attractive candidate for X-PDT in cancer treatment. In this study, we aimed to investigate the effect of Cu-Cy NPs as radiosensitizers on HeLa cervical cancer cells and evaluate their potential therapeutic application in enhancing the efficacy of radiation therapy.
Methods: To assess the intrinsic toxicity of Cu-Cy nanoparticles in HeLa cancer cells, we conducted viability assessments at varying concentrations using MTT assay, both in the presence and absence of radiation exposure. Subsequently, the apoptotic rate of different groups was determined using the Annexin-V/PI staining followed by the flow cytometry analysis, while cell migration was analyzed using a wound healing assay. The collected data underwent assessment through the use of appropriate statistical tests.
Results: The results demonstrated that at a concentration of 25 mg/L, Cu-Cy NPs exhibited no significant inherent toxicity on HeLa cervical cancer cells. However, concentrations of 50 mg/L and above showed a dose-dependent intrinsic toxicity. Notably, significant differences in cell viability were observed at concentrations of 25 mg/L and higher in the presence of radiation compared to non-irradiated groups, indicating enhanced radiosensitivity of the cancer cells. The viability in the NPs alone, radiation alone, and NPs + radiation groups were 93.85%, 90.81%, and 80.46%, respectively, indicating a significant difference between the NPs + radiation group and other groups. The apoptotic rates were 10.39% for radiation alone, 6.05% for NPs alone, and 25.41% for the combination of NPs + radiation, highlighting a significant difference in apoptotic response. Furthermore, the NPs + radiation group showed a significant difference in cell migration compared to radiation or nanoparticles alone, suggesting a potential inhibitory effect on cell migration compared to the individual treatment groups.
Conclusion: In conclusion, the findings of this study suggest that Cu-Cy NPs at low concentrations do not exhibit inherent toxicity and can enhance the radiosensitivity of HeLa cervical cancer cells. The combination of these nanoparticles with radiation yielded significantly reduced cell viability, elevated apoptotic responses, and inhibition of cell migration. These results indicate the potential of Cu-Cy NPs as effective therapeutic agents in enhancing the efficacy of radiation therapy in cervical cancer treatment.