title: Rational design of cancer-targeted selenium nanoparticles to antagonize multidrug resistance in cancer cells.
abstract: 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 receptor-mediated 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.
  
  
  BACKGROUND
  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.
authors: Department of Chemistry, Jinan University, Guangzhou, China.
authors: Ting
authors: T
authors: Liu
authors: Department of Chemistry, Jinan University, Guangzhou, China.
authors: Lilan
authors: L
authors: Zeng
authors: Department of Chemistry, Jinan University, Guangzhou, China.
authors: Wenting
authors: W
authors: Jiang
authors: Department of Chemistry, Jinan University, Guangzhou, China.
authors: Yuanting
authors: Y
authors: Fu
authors: Department of Chemistry, Jinan University, Guangzhou, China.
authors: Wenjie
authors: W
authors: Zheng
authors: Department of Chemistry, Jinan University, Guangzhou, China. Electronic address: tchentf@jnu.edu.cn.
authors: Tianfeng
authors: T
authors: Chen
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D009363:Neoplasm Proteins; D012643:Selenium
keywords: Cancer targeting; Multidrug resistance; Nanodrug delivery; Selenium nanoparticles