文献类型：期刊文献

英文题名：Efficient enzyme-activated therapy based on the different locations of protein and prodrug in nanoMOFs

作者：Wang, Fan[1,2];Yang, Jian[1,2];Li, Yongsheng[1,2];Zhuang, Qixin[1,2];Gu, Jinlou[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Engn Res Ctr Hierarch Nanomat, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Minist Educ, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Shanghai 200237, Peoples R China

年份：2020

卷号：8

期号：28

起止页码：6139

外文期刊名：JOURNAL OF MATERIALS CHEMISTRY B

收录：;EI(收录号：20203609147131);WOS:【SCI-EXPANDED(收录号:WOS:000550975200011)】；

基金：This work was financially supported by the Natural Science Foundation of China (21975072, 51902106, and 51372084), the Natural Science Foundation of Shanghai (18ZR1408700), the Projects of Shanghai Municipality (18JC1410802), the National Key Research and Development Program (2016YFC1102100) and 111 Project (B14018).

语种：英文

外文关键词：Catalyst activity - Biodegradability - Cell death - Controlled drug delivery - Loading - Targeted drug delivery - Chemical activation - Enzyme activity - Cancer cells

摘要：Enzyme-activated prodrug therapy (EAPT) is an effective cancer treatment strategy able to transport non-toxic prodrugs and subsequently convert them into drugs at specific times and locations. However, due to the limitation of easy biodegradability and the membrane-impermeable characteristic of exogenous enzymes, there is a need to exploit suitable carriers for the effective protection and simultaneous delivery of activating enzymes into cancer cells. Herein, hierarchically porous MOFs were employed for the loading of enzyme and prodrug in a single nanocarrier thanks to their different cavity sizes. The simple loading process allows entrapping of horseradish peroxidase (HRP) and a monocarboxyl-containing indole-3-acetic acid (IAA) prodrug with high loading capacities in different spaces, which keeps the catalytic activity of the enzyme perfectly intact and avoids the premature activation of the prodrug. The encapsulatedHRPandIAAexhibit sustained and synchronized release behaviors. Compared to the nativeHRPenzyme, the current MOF nanocarriers not only facilitate enzyme delivery into cellular lysosomes and subsequent endosomal escape, but also effectively release enzyme and prodrug in the intracellular environment within 48 h. Eventually,HRPandIAAloaded MOF nanocarriers cause significant cell death with a low IC(50)of 4.2 mg L-1, while theIAAprodrug alone is non-toxic even at high concentrations. Thus, hierarchically porous MOFs might offer a promising platform for EAPT with a highly consistent spatiotemporal distribution of enzymes and prodrugs in target tissues.