title: Targeted delivery of Dicer-substrate siRNAs using a dual targeting peptide decorated dendrimer delivery system.
abstract: Small interfering RNAs (siRNA) are emerging as novel therapeutic agents, providing competent delivery systems that are available. Dendrimers, a special family of synthetic macromolecules, represent an exciting delivery platform by virtue of their well-defined dendritic structure and unique multivalency and cooperativity confined within a nanoscale volume. Here, we report a Dicer-substrate siRNA (dsiRNA) which, when delivered using a structurally flexible triethanolamine-core poly(amidoamine) dendrimer of generation 5 as the nanocarrier, gives rise to a much greater RNAi response than that produced with conventional siRNA. Further decoration of the dsiRNA/dendrimer complexes with a dual targeting peptide simultaneously promoted cancer cell targeting through interacting with integrins and cell penetration via the interaction with neuropilin-1 receptors, which led to improved gene silencing and anticancer activity. Altogether, our results disclosed here open a new avenue for therapeutic implementation of RNAi using dendrimer nanovector based targeted delivery.
  
  
  BACKGROUND
  This study demonstrates superior therapeutic properties of siRNA when combined with a dendrimer-based targeted nano-delivery system. Similar approaches may eventually gain clinical utility following additional studies determining safety and efficacy.
authors: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, CINaM UMR 7325, Marseille, France.
authors: Xiaoxuan
authors: X
authors: Liu
authors: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, CINaM UMR 7325, Marseille, France; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, P. R. China.
authors: Cheng
authors: C
authors: Liu
authors: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, CINaM UMR 7325, Marseille, France; Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire, UMR 7273, Marseille, France.
authors: Chao
authors: C
authors: Chen
authors: Institut Paoli-Calmettes, Marseille, France.
authors: Mélanie
authors: M
authors: Bentobji
authors: Institut Paoli-Calmettes, Marseille, France.
authors: Francine Azario
authors: FA
authors: Cheillan
authors: Institut Paoli-Calmettes, Marseille, France.
authors: Jeanne Thomassin
authors: JT
authors: Piana
authors: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, P. R. China.
authors: Fanqi
authors: F
authors: Qu
authors: Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM, UMR 1068, Marseille, France; Aix-Marseille Université, Marseille, France; CNRS, UMR 7258, Marseille, France.
authors: Palma
authors: P
authors: Rocchi
authors: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, CINaM UMR 7325, Marseille, France. Electronic address: ling.peng@univ-amu.fr.
authors: Ling
authors: L
authors: Peng
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics; D050091:Dendrimers / Q000737:chemistry*; D005434:Flow Cytometry; D020868:Gene Silencing; D005822:Genetic Vectors; D006801:Humans; D018613:Microscopy, Confocal; D010455:Peptides / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics
chemical_list: D050091:Dendrimers; D010455:Peptides; D034741:RNA, Small Interfering; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Dendrimer; Nanovector; Prostate cancer; Targeted delivery; siRNA