Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy  

作　　者：Yaqiao Li Lingxiao Li Qianhui Jin Tian Liu Jin Sun Yongjun Wang Zhijun Yang Zhonggui He Bingjun Sun 

机构地区：[1]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第2期241-252,共12页亚洲药物制剂科学（英文）

基　　金：financially supported by National Natural Science Foundation of China (no. 81872816);Doctoral Scientific Research Staring Foundation of Liaoning Province (no. 2021BS-130);General Program of Department of Education of Liaoning Province (no. LJKZ0953)

摘　　要：PEGylation has been widely used to improve the pharmacokinetic properties of prodrug self-assembled nanoparticles(prodrug-SANPs).However,the impacts of the amount of PEG on the self-assemble stability,cellular uptake,pharmacokinetics,and antitumor efficacy of prodrug-SANPs are still unknown.Herein,selenoether bond bridged docetaxel dimeric prodrug was synthesized as the model prodrug.Five prodrug-SANPs were designed by using different mass ratios of prodrugs to PEG(W_(prodrug)/W_(DSPE-mPEG2000)=10:0,9:1,8:2,7:3 and 6:4),and defined as Pure drug NPs,9:1NPs,8:2NPs,7:3 NPs and 6:4 NPs,respectively.Interestingly,8:2 NPs formed the most compact nanostructure,thus improving the self-assemble stability and pharmacokinetics behavior.In addition,the difference of these prodrug-SANPs in cellular uptake was investigated,and the influence of PEG on cytotoxicity and antitumor efficacy was also clarified in details.The 8:2 NPs exhibited much better antitumor efficacy than other prodrug-SANPs and even commercial product.Our findings demonstrated the pivotal role of the amount of PEG on prodrug-SANPs.

关 键 词：PEGYLATION PRODRUG Self-assembly nanoparticles DOCETAXEL Oxidation responsive 

分 类 号：R943[医药卫生—药剂学]