Nanoformulation of a Pin1 inhibitor potentiates the efficacy of liposomal doxorubicin in second-line therapy for ovarian cancer.

The second-line therapy for high-grade serous ovarian cancer (HGSOC) patients is generally ineffective. Drug selection is not aimed at improving overall survival, but rather based on residual toxicities, clinical judgment, and patient adherence. Therefore, the identification of more effective and targeted therapeutic strategies is critically needed. The Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) has emerged as a key hallmark of cancer progression and represents a promising therapeutic target in ovarian cancer (OC). VS10, a novel PIN1 inhibitor developed by our group, has shown potent activity against ovarian cancer cell lines. In this study, a drug delivery system for VS10 was developed by formulating the inhibitor into nanocrystals stabilized with human serum albumin. Comprehensive physicochemical characterization of the formulation was performed using spectrophotometric quantification, dynamic light scattering (DLS) with zeta potential analysis, transmission electron microscopy (TEM), X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). The nanocrystals exhibited favorable sustained release kinetics, as confirmed by in vitro release tests. The anticancer activity was further validated through IC50 determinations on OC cell lines, and the therapeutic potential was assessed in vivo using an OC xenograft model. The VS10-loaded nanocrystals significantly inhibited tumor growth, and histopathological analysis confirmed the absence of systemic toxicity. Notably, co-administration with pegylated liposomal doxorubicin, a clinically approved chemotherapeutic agent, produced a synergistic effect, further enhancing tumor suppression. These findings support the potential of VS10, delivered via albumin-stabilized nanocrystals, as a promising second line therapy for OC.