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

作　　者：Zean Li Jun Huang Tao Du Yiming Lai Kaiwen Li Man-Li Luo Dingjun Zhu Jun Wu Hai Huang 

机构地区：[1]Department of Urology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510220,China [2]School of Biomedical Engineering,Sun Yat-sen University,Shenzhen 518107,China [3]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [4]Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [5]Department of Obstetrics and Gynecology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [6]Department of Urology,The Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan People’s Hospital,Qingyuan 511518,China

出　　处：《Chinese Chemical Letters》2022年第5期2496-2500,共5页中国化学快报（英文版）

基　　金：Supported by the National Natural Science Foun-dation of China(Nos.81672550,81974395);Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011437);In-ternational Science and Technology Cooperation Project Plan of Guangdong Province(No.2021A0505030085);Sun Yat-sen Uni-versity Clinical Research 5010 Program(No.2019005);Sun Yat-sen Clinical Research Cultivating Program(No.201702);Guang-dong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation(No.2020B1212060018OF006);Guangdong Provincial Clinical Research Center for Urological Diseases(No.2020B1111170006)to Hai Huang,the National Natural Science Foundation of China(No.51973243);Fundamental Research Funds for the Central Universities(No.191gzd35);International Coop-eration and Exchange of the National Natural Science Founda-tion of China(No.51820105004),Shenzhen Basic Research Project(No.JCYJ20190807155801657);the Project for Science&Technology New Star of Zhujiang in Guangzhou City(No.201906010082).

摘　　要：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±6.7nm)and high NSC23766 loading(8.0%±1.1%)with a more rapid release of NSC23766 at pH 5.0.In vitro cellu-lar 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.Further-more,in vivo studies using PC3-bearing mice demonstrated that NSC23766@8P6 NPs delivered by in-travenous injection not only increased the drug concentration with prolonged retention(96h)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.

关 键 词：Prostate cancer NSC23766 RAC1 Nanoparticle Poly(ester amide) 

分 类 号：TQ317[化学工程—高聚物工业] TB383.1[一般工业技术—材料科学与工程] R737.25[医药卫生—肿瘤]