Nitroxide radical-containing nanoparticles as potential candidates for overcoming drug resistance in epidermoid cancers

作者：Shashni Babita; Alshwimi Abdulaziz; Minami Kentaro; Furukawa Tatsuhiko; Nagasaki Yukio^*

来源：Polymer, 2017, 116: 429-438.

DOI：10.1016/j.polymer.2017.02.052

• Multidrug resistance
• Reactive oxygen species (ROS)
• ROS scavenging
• Nitroxide radical-containing nanoparticles
• Combination chemotherapy

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.

• 出版日期2017-5-5