title: Multifunctional selenium nanoparticles: Chiral selectivity of delivering MDR-siRNA for reversal of multidrug resistance and real-time biofluorescence imaging.
abstract: Herein, chiral selenium nanoparticles (L-SeNPs/D-SeNPs) modified with a dinuclear Ruthenium (II) complex were used to effectively deliver siRNA targeting the MDR1 gene. In this co-delivery system, the luminescent dinuclear Ruthenium (II) complex was developed to act as a gene carrier and anti-tumor drug, while offering luminescent imaging to follow the intracellular trafficking. Interestingly, Ru@L-SeNPs exhibited a stronger protein and pDNA affinity than Ru@D-SeNPs, indicating that chirality may have an effect on pDNA/siRNA binding and biocompatibility. Cisplatin-resistant A549R cells treated with Ru@L-SeNPs-siRNA demonstrated significant downregulation of P-glycoprotein (P-gp) expression, resulting in unprecedented enhanced cytotoxicity through the induction of apoptosis with the involvement of phosphorylation of p53, MAPK and PI3K/Akt signaling pathways. In vivo investigation confirmed that Ru@L-SeNPs-siRNA nanoparticles exhibited high tumor-targeted fluorescence, enhanced anti-tumor efficacy, and decreased systemic toxicity. These results suggest that Ru@L-SeNPs are promising vectors for the delivery of siRNA and for real-time tracking of treatment.
  
  
  BACKGROUND
  In this study, the authors designed bi-functional selenium nanoparticles with specific chirality to deliver siRNA, for targeting tumor MDR1 gene. The underlying ruthenium (II) complex could also offer fluorescence for real-time imaging. This new system has been shown to have enhanced efficacy against drug resistant tumor cells in both in-vitro and in-vivo experiments.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Qingchang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Biology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Dhairya
authors.initials: D
authors.lastname: Bhavsar
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Licong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China. Electronic address: tliuliu@jnu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Guangdong Medical University, Zhanjiang, China.
authors.forename: Lan-mei
authors.initials: LM
authors.lastname: Chen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D012428:Ruthenium / Q000737:chemistry; D012643:Selenium / Q000008:administration & dosage / Q000737:chemistry
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D034741:RNA, Small Interfering; D012428:Ruthenium; D012643:Selenium; D002945:Cisplatin
keywords: Biofluorescence imaging; Chiral selenium nanoparticle; Dinuclear ruthenium complexes; Drug and gene delivery; Multidrug resistance; siRNA