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...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.展开更多
基金Supported by the National Natural Science Foun-dation of China(Nos.81672550,81974395)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011437)+7 种基金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).
文摘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.
