Enhanced activity of a pluronic F127 formulated Pin1 inhibitor for ovarian cancer therapy

Ovarian cancer remains the most lethal gynecological malignancy, characterized by late-stage diagnosis and high recurrence rates. Recent research highlights the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) enzyme as a critical therapeutic target, as it is significantly upregulated in cancer stem cells and drives tumor progression. While the non-covalent inhibitor C17 exhibits potent nanomolar enzymatic activity against Pin1, its therapeutic utility is severely hampered by poor solubility and low cell permeability. To address these pharmacokinetic limitations, this study developed a novel nanoformulation of C17 using the FDA-approved, biocompatible polymer Pluronic F127®. The anticancer efficacy of this delivery system was evaluated across multiple ovarian cancer cell lines and patient-derived tumor organoids (PDTOs), which serve as highly relevant human models for high-grade serous carcinoma. Our results demonstrate that the Pluronic F127® matrix effectively encapsulates C17, enhancing its bioavailability and inhibitory impact on tumor growth. By overcoming the physical barriers to C17 delivery, this nano-based strategy provides a promising approach to improve the treatment of chemoresistant ovarian cancer through targeted Pin1 inhibition.