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

• Published in: Chinese chemical letters Vol. 33; no. 5; pp. 2496 - 2500
• Main Authors: Li, Zean, Huang, Jun, Du, Tao, Lai, Yiming, Li, Kaiwen, Luo, Man-Li, Zhu, Dingjun, Wu, Jun, Huang, Hai
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.05.2022; Department of Urology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510220,China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China; Department of Urology,The Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan People's Hospital,Qingyuan 511518,China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China%Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China; Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China%Department of Urology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510220,China; Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China; Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China%School of Biomedical Engineering,Sun Yat-sen University,Shenzhen 518107,China%Department of Obstetrics and Gynecology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China%Department of Urology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510220,China
• Subjects: Nanoparticle; NSC23766; Poly(ester amide); Prostate cancer; Rac1; Rac1; Nanoparticle; Poly(ester amide); Prostate cancer; NSC23766
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2021.11.078

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 (NSC23766@8P6 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 NSC23766@8P6 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 NSC23766@8P6 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 NSC23766@8P6 NPs can serve as a delivery system that targets the tumor site and is therefore a promising therapeutic approach for PCa treatment. NSC23766-loaded Phe-PEA polymer NPs which synthesized by amino acid-based Phe-PEA polymers displayed high loading capacity with persistent blood circulation, passive tumor-targeting ability, low burst effect and optimal drug in vitro. In consideration of great cytotoxicity and less systemic cytotoxicity in PCa cell lines and xenografts, NSC23766-8P6 NPs could be promising as a novel strategy in the fight against PCa. [Display omitted]