PLGA-PEG-c(RGDfK)-Kushenol E Micelles With a Therapeutic Potential for Targeting Ovarian Cancer.

Background: As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from Sophora flavescens, which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor-targeting nanoparticle system modified with tumor-homing c(RGDfK) peptides. Materials and Methods: In the current study, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-modified with cyclic RGDfK peptide (PLGA-PEG-c(RGDfK))-KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor-active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV-3 cells and xenograft models in BALB/c nude mice. Results: The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV-3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration-dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site. Conclusion: The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.