文献类型：期刊文献

英文题名：Transferrin-targeting pH-responsive and biodegradable mesoporous silica nanohybrid for nitric oxide-sensitized chemotherapy of cancer

作者：Li, Ting[1,2];Cheng, Di[1];Xu, Xiu[1];Wang, Bin[1];Xing, Wenqian[1,2];Xu, Yufang[1];Qian, Xuhong[1];Yang, Youjun[1];Zhu, Weiping[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2025

卷号：246

外文期刊名：COLLOIDS AND SURFACES B-BIOINTERFACES

收录：;EI(收录号：20244817436685);WOS:【SCI-EXPANDED(收录号:WOS:001371467600001)】；

基金：This work was supported by National Natural Science Foundation of China (Grants 21878088, 21476077) , Key projects of Shanghai Science and Technology Commission (18DZ1112703) , Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03-2) and the Research Funds of Happiness Flower ECNU (2020JK2103) .

语种：英文

外文关键词：PH-responsive; Biodegradable mesoporous organosilica; Nitric oxide sensitization; Drug-resistant inhibition

摘要：Weakly acidic pH, low oxygen and high glutathione levels are the main characteristics of tumor cells. Taking advantage of the unique acidic microenvironment of tumor cells, acid-responsive mesoporous organosilica nanoparticles (AMON) were designed for nitric oxide (NO)-sensitized chemotherapy of tumors. AMON served as a nanocarrier co-loaded with a nitric oxide donor (NOD) and chemotherapeutic drug doxorubicin (DOX). Transferrin (Tf) was modified on the surface as a targeting ligand to form NOD&DOX@AMON. In vitro experiments showed that AMON could be completely degraded under acidic conditions (pH 5.0) after 48 h. NOD&DOX@AMON entered cells via transferrin receptor-mediated internalization and degraded in the acidic microenvironment to release its payloads. NOD released NO in presence of one-electron reducing substances like Glutathione (GSH) and ascorbic acid, inhibiting P-glycoprotein(P-gp) function and thereby increasing the intracellular concentration of DOX. In vivo distribution studies revealed that the nanohybrids accumulated maximally in tumor tissue 12 h after intravenous injection and exhibited significant inhibitory effects on HepG2 xenograft tumors. Western blot experiments demonstrated that NOD&DOX@AMON could inhibit the expression of drug resistance-associated proteins and was expected to be employed as a therapeutic approach for drugresistant ttumors.