Nanovoid-confinement and click-activated nanoreactor for synchronous delivery of prodrug pairs and precise photodynamic therapy  

作　　者：Peng Wang Fang Zhou Xia Yin Qingji Xie Guosheng Song Xiao-Bing Zhang 

机构地区：[1]Molecular Science and Biomedicine Laboratory,State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,Hunan University,Changsha 410082,China [2]Key Laboratory of Chemical Biology and Traditional Chinese Medicine(Hunan Normal University),Ministry of Education,Changsha 410082,China

出　　处：《Nano Research》2022年第10期9264-9273,共10页纳米研究（英文版）

基　　金：supported by the National Key R&D Program of China(No.2019YFA0210103);the National Natural Science Foundation of China(No.21974039);China Postdoctoral Science Foundation(Nos.2020TQ0092 and 2020M682537);the Science and Technology Innovation Program of Hunan Province(No.2020RC2019);the Special Funds for the Construction of Innovative Provinces in Hunan Province(No.2019RS1031);the Opening Fund of Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research(Hunan Normal University),the Ministry of Education.

摘　　要：Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer therapy.However,the click and release efficiency of these methods in vivo is limited by the space-time dislocation of bioorthogonal prodrug-trigger pairs within the tumor area,caused by their asynchronous administration and inconsistent accumulation for most delivery systems.We herein created a nanovoid-confinement and click-activated(NCCA)core–shell nanoreactor by incorporating prodrugs within zeolitic imidazolate framework-90(ZIF-90)as core and coating tetrazine-based covalent organic framework(COF)as shell.After surface modification of aptamer polymer,the NCCA nanoreactor enabled the sufficient delivery of photodynamic prodrugs within tumor.Notably,the core of ZIF-90 was decomposed by tumor acidic environment,inducing the high-efficiency activation of photodynamic prodrugs via nanoconfined bioorthogonal reaction with tetrazine-based COF shell.As a result,such photodynamic agents are efficiently and safely accumulated into tumor and specifically activated for precise photodynamic therapy of cancer cells and tumor bearing mice with minimizing toxic side effect.Taken together,such NCCA nanoreactor clearly demonstrates the critical feasibility to realize the synchronous delivery of both prodrugs and triggers for precise treatment,which most of delivery systems are not able to afford.

关 键 词：NANOREACTOR covalent organic framework bioorthogonal reaction PRODRUG photodynamic therapy 

分 类 号：R730.5[医药卫生—肿瘤] TB383[医药卫生—临床医学]