Selenium-driven enhancement of synergistic cancer chemo-/radiotherapy by targeting nanotherapeutics

To overcome drug resistance in hypoxic tumors and the limitations of radiation impedance and radiation dose, we developed a nano-radiosensitizer to improve the efficacy of cancer radiotherapy. We used multifunctional mesoporous silica nanoparticles (MSNs) as the carriers for a novel anticancer selenadiazole derivative (SeD) and modified its surface with folic acid (FA) to enhance its cervical cancer-targeting effects, forming the nanosystem named SeD@MSNs-FA. Upon radiation, SeD@MSNs-FA inhibits the growth of cervical cancer cells by inducing apoptosis through the death receptor-mediated apoptosis pathway and S phase arrest, significantly improving the sensitivity of cervical cancer cells to X-ray radiation. The combined activity of SeD@MSN-FA and radiation can promote excessive production of intracellular reactive oxygen species (ROS) and induce cell apoptosis by affecting p53, protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) pathways. Furthermore, SeD@MSNs-FA can effectively inhibit tumor growth of xenografted HeLa tumors in nude mice. The toxicity analysis of SeD@MSNs-FA nanoparticles in vivo and the histological analysis performed in the mouse model showed that under the current experimental conditions, the nanoparticles induced no significant damage to the heart, liver, spleen, lungs, kidneys, or other major organs. Taken together, this study provides a translational nanomedicine-based strategy for the simultaneous chemo- and radiotherapy of cervical cancer and sheds light on potential mechanisms that can be used to overcome radiotherapeutic resistance.