Combination treatments are most effective when targeting different cancer survival and growth pathways. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. In this study, we developed a light-activatable nanocomplex that selectively and simultaneously deliver three clinically relevant therapeutic agents at a synergistic drug ratio to destroy ovarian cancer cells, while sparing normal tissues.
Ovarian cancer typically spreads throughout the peritoneal cavity, and despite standard of care treatments (surgical debulking and chemotherapy), the five-year relative survival rate remains below 50%. The use of antibody-photosensitizer conjugates (photoimmunotherapy) has emerged as a promising modality to achieve targeted photosensitizer delivery to ovarian cancer cells. In this study, we investigate epithelial growth factor (EGFR)-targeted PIT coupled with inhibition of prostaglandin E2 receptor 4 (EP4), a G-coupled-receptor that contributes to cancer progression and intracellularly transactivates EGFR. This potent triple combination significantly attenuates the metastatic behavior of ovarian cancer cells through simultaneously inducing photochemical damage and modulating protein expression.
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