期刊
POLYMER
卷 116, 期 -, 页码 429-438出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.polymer.2017.02.052
关键词
Multidrug resistance; Reactive oxygen species (ROS); ROS scavenging; Nitroxide radical-containing nanoparticles; Combination chemotherapy
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [25220203]
- Grants-in-Aid for Scientific Research [16K15628] Funding Source: KAKEN
Multidrug resistance in cancer cells contributes to the failure of conventional chemotherapy in more than 90% of cancer patients (metastatic). This is attributed to reactive oxygen species (ROS)-regulated drug efflux proteins, P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). In this study, we focused on overcoming multidrug resistance with a therapeutic application of ROS-scavenging nitroxide radical-containing nanoparticles, RNPN (pH-sensitive) and RNPO (pH-insensitive), in combination with the conventional chemotherapeutic drug, doxorubicin (Dox), in drug-resistant epidermoid cancer cell lines, KB-C2 (P-gp expressing) and KB/MRP (MRP1 expressing). We confirmed that the combination treatment with RNPs increased Dox uptake in multidrug-resistant cancer cells, which further enhanced cell cytotoxicity. The abrogation of the crucial ROS signaling was confirmed with RNP treatment, which deterred ROS-regulated drug efflux protein (P-gp and MRP1) expression, resulting in the sensitization of resistant cells to Dox. These results establish ROS-scavenging RNPs as potential therapeutic candidates to overcome drug resistance in multidrug-resistant cancers. (C) 2017 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据