Dietmar Lerche

Silica-Iron Oxide Magnetic Nanoparticles Modified for Gene Delivery: A Search for Optimum and Quantitative Criteria

To optimize silica-iron oxide magnetic nanoparticles with surface phosphonate groups decorated with 25-kD branched polyethylenimine (PEI) for gene delivery. 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. 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 r2* relaxivity values (>600xa0s−1(mM Fe)−1) for the free and cell-internalized particles. 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.ABSTRACTPurposeTo optimize silica-iron oxide magnetic nanoparticles with surface phosphonate groups decorated with 25-kD branched polyethylenimine (PEI) for gene delivery.MethodsSurface 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.ResultsModerate 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 r2* relaxivity values (>600xa0s−1(mM Fe)−1) for the free and cell-internalized particles.ConclusionsSurface 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.

Magnetophoretic Velocity Determined by Space- and Time-Resolved Extinction Profiles

Magnetophoretic velocity of magnetic nano-objects for biomedical applications was characterized by measuring space- and time-resolved extinction profiles (STEP-Technology) using a customized LUMiReader device equipped with a set of permanent magnets (STEP-MAG). The resulting magnetic fields and gradients in a sample volume enable the operator to choose measurement conditions for magnetic micro- and nanoparticles and their assemblies. The dependence of magnetophoretic velocity on concentration and optical wavelengths indicated assembly of the nano-objects upon magnetophoresis. The method has potential applications in biomedicine to develop advanced materials and protocols for cell separation, tissue engineering, and drug/nucleic acid targeting.