Silica-iron oxide magnetic nanoparticles modified for gene delivery: a search for optimum and quantitative criteria

Pharm Res. 2012 May;29(5):1344-65. doi: 10.1007/s11095-011-0661-9. Epub 2012 Jan 6.

Abstract

Purpose: To optimize silica-iron oxide magnetic nanoparticles with surface phosphonate groups decorated with 25-kD branched polyethylenimine (PEI) for gene delivery.

Methods: Surface composition, charge, colloidal stabilities, associations with adenovirus, magneto-tranduction efficiencies, cell internalizations, in vitro toxicities and MRI relaxivities were tested for the particles decorated with varying amounts of PEI.

Results: Moderate PEI-decoration of MNPs results in charge reversal and destabilization. Analysis of space and time resolved concentration changes during centrifugation clearly revealed that at >5% PEI loading flocculation gradually decreases and sufficient stabilization is achieved at >10%. The association with adenovirus occurred efficiently at levels over 5% PEI, resulting in the complexes stable in 50% FCS at a PEI-to-iron w/w ratio of ≥7%; the maximum magneto-transduction efficiency was achieved at 9-12% PEI. Primary silica iron oxide nanoparticles and those with 11.5% PEI demonstrated excellent r(2)* relaxivity values (>600 s(-1)(mM Fe)(-1)) for the free and cell-internalized particles.

Conclusions: Surface decoration of the silica-iron oxide nanoparticles with a PEI-to-iron w/w ratio of 10-12% yields stable aqueous suspensions, allows for efficient viral gene delivery and labeled cell detection by MRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cell Line
  • Colloids / chemistry
  • Drug Stability
  • Ferric Compounds / chemistry*
  • Gene Transfer Techniques*
  • Genetic Vectors / chemistry*
  • Genetic Vectors / genetics
  • Humans
  • Lentivirus / genetics
  • Magnetic Resonance Imaging
  • Magnetics*
  • Mice
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Nanoparticles / chemistry*
  • Polyethyleneimine / chemistry
  • Rats
  • Silicon Dioxide / chemistry*
  • Surface Properties
  • X-Ray Diffraction

Substances

  • Colloids
  • Ferric Compounds
  • ferric oxide
  • Silicon Dioxide
  • Polyethyleneimine