Facile synthesis of size-tunable stable nanoparticles via click reaction for cancer drug delivery

作     者：CAO Ming LIU XiangRui TANG JianBin SUI MeiHua SHEN YouQing 

作者机构：Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering of Zhejiang University Department of Chemical and Biological Engineering Zhejiang University 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2014年第57卷第4期

页      面：633-644页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(21104065 and 21274125) the National Basic Research Program of China(2014CB931900) the Major Research Plan of the National Natural Science Foundation of China(2014CB931900) 

主　　题：crosslinked nanoparticles facile synthesis size effect pharmacokinetics tumor targeting 

摘      要：The stability and size of polymeric nanoparticles are two of the most important parameters determining their pharmacokinetics and tumor/drug accumulation efficiency in cancer-drug delivery. Herein, we report a facile one-pot synthesis of crosslinked nanoparticles(CNPs) with tunable sizes and polyethylene glycol(PEG) shells via click reactions. Simply by adjusting the contents of the macromonomer(PEG monoacrylate) in its reaction with ethylene diacrylate and a crosslinker containing hexa-thiols groups, the sizes of the resulting PEGylated crosslinked nanoparticles could be easily tuned from 10 to 90 nm. These nanoparticle cores could encapsulate hydrophobic drugs such as doxorubicin(DOX), and the unreacted thiol and acrylate groups could be used for drug conjugation or labeling. Thus, the nanoparticles provide a multifunctional platform for drug delivery. In vivo studies showed that the larger nanoparticles(about 83.7 nm) had a much longer blood-circulation time and better tumor-targeting efficiency. One of our most important findings was that the drug encapsulated in the crosslinked nanoparticles, even though little was released at pH 7.4 under in vitro conditions, had much faster blood clearance than the nanoparticles carrier, suggesting that drug release in the bloodstream was significant.