Omeprazole-Loaded Gold-Coated Copper Nanosensitizers for Photothermal-Radiotherapy of Cervical Cancer Cells

Cervical cancer is the second most common cancer affecting women, and it is also the only cancer that can be cured completely, when detected early. However, the available current treatment modalities do not ensure a complete cancer remission. Metal-based nanoparticles have been actively studied for anticancer effects, of which copper is affordable and has a redox potential. But, there is a possibility of copper toxicity in the body that is associated with these treatment modalities. Hence, developing a multimodal approach that combines different treatment modalities is essential to using copper within the nontoxic range and achieving an enhanced anticancer effect. This could be achieved by a synergy between copper overload and radiation-based therapies (ionizing and nonionizing). Omeprazole is an FDA-approved drug that is widely used in the treatment of ulcers. Furthermore, omeprazole is also a copper exporter inhibitor that could be used to cause copper overload in cancer cells. In this perspective, we have developed a gold-coated copper-based nanosystem loaded with omeprazole (Au-CBO) that would aid in leveraging the potential of omeprazole to cause copper overload in cancer cells and the ability of the gold coating to cause photothermal-based hyperthermia/radiosensitization of cancer cells to cause enhanced anticancer effects in the cervical cancer cell line, HeLa. Au-CBO nanoparticles showed good biocompatibility and hemocompatibility. The developed Au-CBO nanosystem showed excellent anticancer activity in HeLa cells with both PTT (87% cytotoxicity) and radiation-mediated therapy (72% cytotoxicity) by ROS-induced lipid peroxidation. The nanoparticle also exhibited significant anticancer effects in 3D spheroids of HeLa cells, proving its ability to act as a potential sensitizer for application in both photothermal therapy(PTT) and radiation-based therapy.