title: Cancer-targeting siRNA delivery from porous silicon nanoparticles.
abstract: OBJECTIVE
  Porous silicon nanoparticles (pSiNPs) with tunable pore size are biocompatible and biodegradable, suggesting that they are suitable biomaterials as vehicles for drug delivery. Loading of small interfering RNA (siRNA) into the pores of pSiNPs can protect siRNA from degradation as well as improve the cellular uptake. We aimed to deliver MRP1 siRNA loaded into pSiNPs to glioblastoma cells, and to demonstrate downregulation of MRP1 at the mRNA and protein levels.
  
  
  METHODS
  50-220 nm pSiNPs with an average pore size of 26 nm were prepared, followed by electrostatic adsorption of siRNA into pores. Oligonucleotide loading and release profiles were investigated; MRP1 mRNA and protein expression, cell viability and cell apoptosis were studied.
  
  
  RESULTS
  Approximately 7.7 µg of siRNA was loaded per mg of pSiNPs. Cells readily took up nanoparticles after 30 min incubation. siRNA-loaded pSiNPs were able to effectively downregulate target mRNA (~40%) and protein expression (31%), and induced cell apoptosis and necrosis (33%).
  
  
  CONCLUSIONS
  siRNA loaded pSiNPs downregulated mRNA and protein expression and induced cell death. This novel siRNA delivery system may pave the way towards developing more effective tumor therapies.
authors.affiliation: Mawson Institute, University of South Australia, Mawson Lakes, Adelaide, SA 5095, Australia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wan
authors.forename: Sinoula
authors.initials: S
authors.lastname: Apostolou
authors.forename: Roman
authors.initials: R
authors.lastname: Dronov
authors.forename: Bryone
authors.initials: B
authors.lastname: Kuss
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Voelcker
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012825:Silicon / Q000737:chemistry*; D018629:Spectrometry, Mass, Secondary Ion; D055672:Static Electricity
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D012825:Silicon
keywords: MRP1; ToF-SIMS; drug delivery; glioblastoma; porous silicon nanoparticles; siRNA