Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. The Rac1-GTP inhibitor NSC23766 has been shown to suppress PCa growth. However, these therapies have low tumor-targeting efficacy in vivo. Therefore, it is essential to produce a drug delivery system that specifically targets the tumor site. Herein, novel l-phenylalanine-based poly(ester amide) (Phe-PEA) polymers were synthesized and loaded with NSC23766 ([email protected] NPs), which had a small particle size (162.3 ± 6.7 nm) and high NSC23766 loading (8.0% ± 1.1%) with a more rapid release of NSC23766 at pH 5.0. In vitro cellular uptake and cytotoxicity assays demonstrated that [email protected] NPs were rapidly taken up by PC3 cells and showed significant effects of PCa cell proliferation inhibition and G2/M phase arrest. Furthermore, in vivo studies using PC3-bearing mice demonstrated that [email protected] NPs delivered by intravenous injection not only increased the drug concentration with prolonged retention (96 h) at the tumor site, but also inhibited tumor growth and induced apoptosis. In conclusion, we have discovered that [email protected] NPs can serve as a delivery system that targets the tumor site and is therefore a promising therapeutic approach for PCa treatment.