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

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An Erratum to this article was published on 03 February 2012

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 r2* 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.

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Abbreviations

ATCC:

American Type Culture Collection

DMEM:

Dulbecco’s modified Eagle’s medium

EDTA:

Ethylenediaminetetraacetic acid

FCS:

fetal calf serum

ME-FFE:

multi-echo gradient echo

MNP:

magnetic nanoparticles

mPDAC:

mouse pancreatic ductal adenocarcinoma

MRI:

magnetic resonance imaging

PBS:

Dulbecco’s phosphate buffered saline

PEI:

polyethylenimine

SIO-MNP:

silica-iron oxide magnetic nanoparticle

SiOx :

silica-like coating of the iron oxide nanoparticles

TEM:

Transmission Electron Microscopy

TEOS:

tetraethyl orthosilicate

THPMP:

3-(trihydroxysilyl) propylmethylphosphonate

TU:

transducing units

VP:

virus particle

XPS:

X-ray photoelectron spectroscopy

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Authors and Affiliations

  1. Institute of Experimental Oncology and Therapy Research, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstrasse 22, 81675, Munich, Germany

    Olga Mykhaylyk, Yolanda Sanchez-Antequera, Sabine Brandt, Martina Anton & Christian Plank

  2. LUM GmbH, Rudower Chaussee 29 (OWZ), 12489, Berlin, Germany

    Titus Sobisch & Dietmar Lerche

  3. Department of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Isabella Almstätter, Marcus Settles & Rickmer Braren

  4. Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, 81377, Germany

    Markus Döblinger

  5. Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, 10587, Berlin, Germany

    Dietmar Eberbeck

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  1. Olga Mykhaylyk
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  2. Titus Sobisch
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Correspondence to Olga Mykhaylyk.

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Mykhaylyk, O., Sobisch, T., Almstätter, I. et al. Silica-Iron Oxide Magnetic Nanoparticles Modified for Gene Delivery: A Search for Optimum and Quantitative Criteria. Pharm Res 29, 1344–1365 (2012). https://doi.org/10.1007/s11095-011-0661-9

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