Integrated prodrug micelles with two-photon bioimaging and pH-triggered drug delivery for cancer theranostics  

作　　者：Hong Xu Boxuan Ma Jizhou Jiang Sutong Xiao Rongrong Peng Weihua Zhuang Gaocan Li Yunbing Wang 

机构地区：[1]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China [2]College of Polymer Science and Engineering,Sichuan University,Chengdu 610064,China

出　　处：《Regenerative Biomaterials》2020年第2期171-180,共10页再生生物材料（英文版）

基　　金：supported by the National Natural Science Foundation of China(Projects No.21502129);the National 111 Project of Introducing Talents of Discipline to Universities(No.B16033);China Postdoctoral Science Foundation Funded Project(Nos.2017M612956,2018T110969);the State Key Laboratory of Polymer Materials Engineering(No.sklpme2018-3-05)。

摘　　要：Nanodrug carriers with fluorescence radiation are widely used in cancer diagnosis and therapy due to their real-time imaging,less side effect,better drug utilization as well as the good bioimaging ability.However,traditional nanocarriers still suffer from unexpectable drug leakage,unsatisfactory tumor-targeted drug delivery and shallow imaging depth,which limit their further application in cancer theranostics.In this study,an integrated nanoplatform is constructed by polymeric prodrug micelles with two-photon and aggregation-induced emission bioimaging,charge reversal and drug delivery triggered by acidic pH.The prodrug micelles can be self-assembled by the TPPEI(DA/DOX)-PEG prodrug polymer,which consists of the two-photon fluorophore(TP),dimethylmaleic anhydride(DA)grafted polyethyleneimine(PEI)and polyethylene glycol(PEG).The PEG segment,DOX and DA are bridged to polymer by acid cleavable bonds,which provides the micelles a‘stealth’property and a satisfactory stability during blood circulation,while the outside PEG segment is abandoned along with the DA protection in the tumor acidic microenvironment,thus leading to charge reversal-mediated accelerated endocytosis and tumor-targeted drug delivery.The great antitumor efficacy and reduced side effect of these pH-sensitive prodrug micelles are confirmed by antitumor assays in vitro and in vivo.Meanwhile,these micelles exhibited great deep-tissue two-photon bioimaging ability up to 150 lm in depth.The great antitumor efficacy,reduced side effect and deep two-photon tissue imaging make the TP-PEI(DA/DOX)-PEG prodrug micelles would be an efficient strategy for theranostic nanoplatform in cancer treatment.

关 键 词：aggregation-induced emission TWO-PHOTON PH-SENSITIVE charge reversal drug delivery system 

分 类 号：R730.5[医药卫生—肿瘤]