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    ABSTRACT: Oncolytic viruses are promising new agents in cancer therapy. Success of tumor lysis is often hampered by low intra-tumoral titers due to a strong anti-viral host immune response and insufficient tumor targeting. Previous work on the co-assembly of oncolytic virus particles (VPs) with magnetic nanoparticles (MNPs) was shown to provide shielding from inactivating immune response and improve targeting by external field gradients. In addition, MNPs are detected by magnet resonance imaging (MRI) enabling non-invasive therapy monitoring. In this study two selected core-shell type iron oxide MNPs were assembled with adenovirus (Ad) or vesicular stomatitis virus (VSV). The selected MNPs were characterized by high r2 and r2 (*) relaxivities and thus could be quantified non-invasively by 1.5 and 3.0 tesla MRI with a detection limit below 0.001 mM iron in tissue-mimicking phantoms. Assembly and cell internalization of MNP-VP complexes resulted in 81 - 97 % reduction of r2 and 35 - 82 % increase of r2 (*) compared to free MNPs. The relaxivity changes could be attributed to the clusterization of particles and complexes shown by transmission electron microscopy (TEM). In a proof-of-principle study the non-invasive detection of MNP-VPs by MRI was shown in vivo in an orthotopic rat hepatocellular carcinoma model. In conclusion, MNP assembly and compartmentalization have a major impact on relaxivities, therefore calibration measurements are required for the correct quantification in biodistribution studies. Furthermore, our study provides first evidence of the in vivo applicability of selected MNP-VPs in cancer therapy.
    Theranostics 01/2015; 5(7):667-85. DOI:10.7150/thno.10438 · 7.83 Impact Factor
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    ABSTRACT: To explore the potential of magnetofection in delivering pDNA to primary mouse embryonic fibroblasts (PMEFs) and porcine fetal fibroblasts (PFFs) and investigate an effect of magnetic cell labeling on transfection efficacy. The formulation and a dose of the magnetic vector were optimized. The efficacy of the procedure was quantified by vector internalization, transgene expression and cell iron loading upon specific labeling with Ab-conjugated magnetic beads or non-specific labeling with MNPs. Up to sixty percent of PMEF and PFF cells were transfected at low pDNA doses of 4-16 pg pDNA/cell. Specific labeling of the PMEFs with MNPs, resulted in a 3- and 2-fold increase in pDNA internalization upon magnetofection and lipofection, respectively, that yielded a 2-4-fold increase in percent of transgene-expressing cells. Non-specific cell labeling had no effect on the efficacy of the reporter expression, despite the acquisition of similar magnetic moments per cell. In PFFs, specific magnetic labeling of the cell surface receptors inhibited internalization and transfection efficacy. Magnetic labeling of cell-surface receptors combined with the application of an inhomogenous magnetic field (nanomagnetic activation) can affect the receptor-mediated internalization of delivery vectors and be used to control nucleic acid delivery to cells.
    Pharmaceutical Research 07/2014; 32(1). DOI:10.1007/s11095-014-1448-6 · 3.95 Impact Factor
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    ABSTRACT: Dispersion based products have applications in every area of life. During formulation of new products the dispersion properties have to be adjusted to obtain the desired stability, textural and rheological properties. Most often stable colloidal dispersions are required, sometime however, weak flocculation is purposely induced to adjust structural properties. In other cases strong flocculation is helpful for dispersion separation. From this it is evident that classification of the state of a dispersion regarding flocculation (net attractive particle interaction) and quantification of its degree are necessary and routine tasks in every day formulation and optimization work. Zeta potential is commonly used to predict the stability of virtually all colloidal dispersions. This neglects that the Zeta potential concept is limited to classical electrostatically stabilized dispersions. It has to be emphasized, however, that nowadays new dispersion products are stabilized by different approaches (e.g. by steric or rheological stabilization). Sedimentation analysis by multisample analytical centrifugation with photometric detection is a rather simple but powerful and high throughput method to characterize the dispersed state/degree of particle interaction. Visualization of in situ separation behaviour allows for the classification and differentiation between the various instability phenomena such as swarm sedimentation (stable dispersion) and zone sedimentation (flocculation, agglomeration). Even more, complex systems with subfractions of particles exhibiting a different behaviour can also be analyzed. Sedimentation behaviour of different dispersions made from plain or decorated nanoparticles as a function of pH of the continuous phase is presented and analyzed in terms of the degree and type of flocculation and compared with predictions based on Zeta potential data. Results demonstrate that contrary to measured Zeta potential the colloidal stability of the dispersed particles and the degree of particle flocculation/agglomeration were always well predicted by the sedimentation behaviour.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 01/2013; DOI:10.1016/j.colsurfa.2012.10.015 · 2.35 Impact Factor