Silica-iron oxide magnetic nanoparticles modified for gene delivery: a search for optimum and quantitative criteria.
OBJECTIVE
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.
Institute of Experimental Oncology and Therapy Research, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstrasse 22, 81675 Munich, Germany. olga.mykhaylyk@lrz.tu-muenchen.de
Olga
O
Mykhaylyk
Titus
T
Sobisch
Isabella
I
Almstätter
Yolanda
Y
Sanchez-Antequera
Sabine
S
Brandt
Martina
M
Anton
Markus
M
Döblinger
Dietmar
D
Eberbeck
Marcus
M
Settles
Rickmer
R
Braren
Dietmar
D
Lerche
Christian
C
Plank
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003102:Colloids / Q000737:chemistry; D004355:Drug Stability; D005290:Ferric Compounds / Q000737:chemistry*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties; D014961:X-Ray Diffraction
D003102:Colloids; D005290:Ferric Compounds; C000499:ferric oxide; D012822:Silicon Dioxide; D011094:Polyethyleneimine