title: A novel polyethyleneimine-coated adeno-associated virus-like particle formulation for efficient siRNA delivery in breast cancer therapy: preparation and in vitro analysis.
abstract: BACKGROUND
  Systemic delivery of small interfering RNA (siRNA) is limited by its poor stability and limited cell-penetrating properties. To overcome these limitations, we designed an efficient siRNA delivery system using polyethyleneimine-coated virus-like particles derived from adeno-associated virus type 2 (PEI-AAV2-VLPs).
  
  
  METHODS
  AAV2-VLPs were produced in insect cells by infection with a baculovirus vector containing three AAV2 capsid genes. Using this method, we generated well dispersed AAV2-VLPs with an average diameter of 20 nm, similar to that of the wild-type AAV2 capsid. The nanoparticles were subsequently purified by chromatography and three viral capsid proteins were confirmed by Western blot. The negatively charged AAV2-VLPs were surface-coated with PEI to develop cationic nanoparticles, and the formulation was used for efficient siRNA delivery under optimized transfection conditions.
  
  
  RESULTS
  PEI-AAV2-VLPs were able to condense siRNA and to protect it from degradation by nucleases, as confirmed by gel electrophoresis. siRNA delivery mediated by PEI-AAV2-VLPs resulted in a high transfection rate in MCF-7 breast cancer cells with no significant cytotoxicity. A cell death assay also confirmed the efficacy and functionality of this novel siRNA formulation towards MCF-7 cancer cells, in which more than 60% of cell death was induced within 72 hours of transfection.
  
  
  CONCLUSIONS
  The present study explores the potential of virus-like particles as a new approach for gene delivery and confirms its potential for breast cancer therapy.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.forename: Arghya
authors.initials: A
authors.lastname: Paul
authors.forename: Sana
authors.initials: S
authors.lastname: Abbasi
authors.forename: Parminder S
authors.initials: PS
authors.lastname: Chahal
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Mena
authors.forename: Johnny
authors.initials: J
authors.lastname: Montes
authors.forename: Amine
authors.initials: A
authors.lastname: Kamen
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use*; D014162:Transfection
chemical_list: D036022:Capsid Proteins; D004337:Drug Carriers; D034741:RNA, Small Interfering; D011094:Polyethyleneimine