Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766
Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766
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DOI：
10.1016/j.cclet.2021.11.078
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发表时间：
2022-04-27
影响因子：
9.1
通讯作者：
Huang, Hai
中科院分区：
文献类型：
--
作者：
Li, Zean;Huang, Jun;Huang, Hai
前列腺癌(PCA)是男性第二常见的癌症。Rac1-GTP抑制剂NSC23766已被证明可以抑制PCa的生长。然而，这些治疗方法在体内的肿瘤靶向效率较低。因此，生产一种针对肿瘤部位的药物输送系统是至关重要的。本文合成了一种新型的L-苯丙氨酸基聚(酯-酰胺)聚合物，并将其负载到NSC23766(NSC23766@8P6NPs)中，NSC23766具有较小的粒径(162.3+/-6.7 nm)和较高的负载量(8.0%+/-1.1%)，在pH值为5.0时，NSC23766具有较快的释放速度。体外细胞摄取和细胞毒实验表明，NSC23766@8P6纳米粒能迅速被PC3细胞摄取，并显示出明显的抑制PC3细胞增殖和G2/M期停滞的作用。此外，用PC3荷瘤小鼠进行的体内研究表明，静脉注射NSC23766@8P6纳米粒不仅增加了药物浓度，延长了药物在肿瘤部位的滞留时间(96h)，而且还抑制了肿瘤生长，诱导了细胞凋亡。总之，我们发现NSC23766@8P6 NPs可以作为靶向肿瘤部位的递送系统，因此是治疗前列腺癌的一种有前途的治疗方法。(C)爱思唯尔公司代表中国化学会和中国医学科学院中药研究所出版的《2021年》。
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. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.