文献类型：期刊文献

英文题名：Glucose Oxidase-Based pH/ROS Dual-Sensitive Nanoparticles for Tumor Starvation and Oxidative Therapy

作者：Chen, Miaoxin[1,2];Li, Gaoyang[1,2];Li, Mengli[1,2];Xu, Shouhong[1,2];Liu, Honglai[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China

年份：2024

卷号：7

期号：16

起止页码：18932

外文期刊名：ACS APPLIED NANO MATERIALS

收录：;EI(收录号：20243316870849);WOS:【SCI-EXPANDED(收录号:WOS:001289099000001)】；

基金：This work was supported by the National Natural Science Foundation of China (22078087) and the Fundamental Research Funds for the Central Universities (2022ZFJH004).

语种：英文

外文关键词：Glucose oxidase; Dual-sensitivity; Nanoparticles; Intracellular delivery; Antitumor

摘要：Cancer cells with their distinct energy supply and metabolic patterns offer unique opportunities for targeted therapy development. This study presents pH/ROS dual-responsive enzyme-carrying nanoparticles for efficient starvation and oxidative therapy in cancer treatment. The nanoparticles, composed of zeolitic imidazolate framework-8 (ZIF-8), glucose oxidase (GOx), and hyaluronic acid (HA), were designed to leverage the unique metabolic characteristics of cancer cells. GOx was covalently modified onto HA to create HA-GOx, demonstrating enhanced enzymatic activity and thermal stability compared with free GOx. The nanoparticles ZIF@HA(gel)-GOx were then synthesized by adsorbing HA-GOx onto ZIF-8 and crosslinking with a ROS-sensitive crosslinker, acetone-[bis-(2-amino-ethyl)-dithioacetal] (TK). The enzymatic properties of ZIF@HA(gel)-GOx in solution and in cells were comparable to those of free GOx, and both could consume glucose to catalyze the reaction. The produced H2O2 could decrosslink the gel layer of ZIF@HA(gel)-GOx, and the produced gluconic acid could degrade the ZIF-8 core, eventually leading to the complete disassembly of ZIF@HA(gel)-GOx. Cytotoxicity assays revealed that GOx-carrying nanoparticles exhibited superior cytotoxicity to DOX carriers and could effectively eliminate cancer cells with minimal dosage. The findings provide a scientific rationale for the use of enzyme-based therapies in the treatment of various diseases.