期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 11, 期 4, 页码 947-958出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.01.009
关键词
Multidrug resistance; Nanodrug delivery; Cancer targeting; Selenium nanoparticles
资金
- National High Technology Research and Development Program of China [SS2014AA020538]
- Science Foundation for Distinguished Young Scholars of Guangdong Province [S2013050014667]
- Foundation for High-level Talents in Higher Education of Guangdong
- Research Fund for the Doctoral Program of Higher Education of China [20114401110004]
- Shenzhen Basic Research Grant [JCYJ20130401152508660]
- Yang Fan Innovative & Entrepreneurial Research Team Project [201312H05]
- Natural Science Foundation of China
Multidrug resistance is one of the greatest challenges in cancer therapy. Herein we described the synthesis of folate (FA)-conjugated selenium nanoparticles (SeNPs) as cancer-targeted nano-drug delivery system for ruthenium polypyridyl (RuPOP) exhibits strong fluorescence, which allows the direct imaging of the cellular trafficking of the nanosystem. This nanosystem could effectively antagonize against multidrug resistance in liver cancer. FA surface conjugation significantly enhanced the cellular uptake of SeNPs by FA receptormediated endocytosis through nystain-dependent lipid raft-mediated and clathrin-mediated pathways. The nanomaterials overcame the multidrug resistance in R-HepG2 cells through inhibition of ABC family proteins expression. Internalized nanoparticles triggered ROS overproduction and induced apoptosis by activating p53 and MAPKs pathways. Moreover, FA-SeNPs exhibited low in vivo acute toxicity, which verified the safety and application potential of FA-SeNPs as nanodrugs. This study provides an effective strategy for the design of cancer-targeted nanodrugs against multidrug resistant cancers. From the Clinical Editor: In the combat against hepatocellular carcinoma, multidrug resistance remains one of the obstacles to be overcome. The authors designed and synthesized folate (FA)-conjugated selenium nanoparticles (SeNPs) with enhanced cancer-targeting capability. This system carried ruthenium polypyridyl (RuPOP), an efficient metal-based anti-cancer drug with strong fluorescence. It was shown that this combination was effective in antagonizing against multidrug resistance in vitro. (C) 2015 Elsevier Inc. All rights reserved.
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