A tumor-targeted heptamethine cyanine dye induces suppression of progesterone receptor activity to treat hormone receptor-positive breast cancer.

Background: A primary treatment of hormone receptor-positive breast cancer is the pharmacological inhibition of hormone receptors by blocking the effects of estrogen and/or progesterone. Methods: In MCF-7 xenograft tumors known as estrogen-sensitive breast cancer, a hydrophilic near-infrared (NIR) heptamethine cyanine dye (named CA800-PR) induced Golgi fragmentation and suppressed only progesterone receptor protein expression, regardless of estrogen receptors. Results: In this study, CA800-PR was newly developed for the treatment of hormone receptor-positive breast cancer unlike conventional drugs such as tamoxifen and aromatase inhibitors. Since the intracellular stress induced by CA800-PR led to the production of pro-inflammatory cytokines, we confirmed a significant increase in the presence of antitumor/pro-inflammatory MHC class II+ CD80+ M1-type macrophages during the course of treatment. Comparing with the traditional hormone therapies aimed at controlling tumor growth or preventing recurrence post-surgery, the tumor-targeted NIR fluorescent dye CA800-PR alone can be effectively used as a multifunctional antitumor agent directly inducing apoptosis in both MCF-7 cells and xenograft tumors. Conclusion: This work provides a promising alternative to hormone therapy-related breast cancer for future clinical applications.