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Shanehsazzadeh S.,Nuclear Science and Technology Research Institute, Iran | Gruettner C.,Micromod Partikeltechnologie GmbH | Lahooti A.,Tehran University of Medical Sciences | Mahmoudi M.,Tehran University of Medical Sciences | And 4 more authors.
Contrast Media and Molecular Imaging | Year: 2015

MUC1 antigen is recognized as a high-molecular-weight glycoprotein that is unexpectedly over-expressed in human breast and other carcinomas. In contrast, C595 a monoclonal antibody (mAb) against the protein core of the human urinary epithelial machine, is commonly expressed in breast carcinomas. The aim of this study was to conjugate ultra-small super paramagnetic iron oxide nanoparticles (USPIO) with C595 mAb, in order to detect in vivo MUC1 expression. A dual contrast agent (the C595 antibody-conjugated USPIO labeled with 99mTc) was prepared for targeted imaging and therapy of anti-MUC1-expressing cancers. The C595 antibody-conjugated USPIO had good stability and reactivity in the presence of blood plasma at 37°C. No significant differences were observed in immunoreactivity results between conjugated and nonconjugated nanoparticles. The T1 and T2 measurements show >79 and 29% increments (for 0.02mg/ml iron concentrations) in T1 and T2 values for USPIO-C595 in comparison with USPIO, respectively. The nanoprobes showed the interesting targeting capability of finding the MUC1-positive cell line in vitro. However, we found disappointing in vivo results (i.e. very low accumulation of nanoprobes in the targeted site while >80% of the injected dose per gram was taken up by the liver and spleen), not only due to the coverage of targeting site by protein corona but also because of absorption of opsonin-based proteins at the surface of nanoprobes. © 2014 John Wiley & Sons, Ltd. Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-3 | Award Amount: 7.73M | Year: 2012

DARTRIX, DARPin Targeted RX (therapy) is a multidisciplinary collaborative project that will develop high-affinity protein scaffolds to create a new generation of targeted therapeutics for the treatment of glioblastoma. There is great need; glioblastoma is virtually incurable and most patients die within 12 months of diagnosis. DARPins are small, non-immunoglobulin human protein scaffolds that bind specific targets with exceptionally high-affinity. DARPins are amenable to GMP production and to scale-up. They are remarkably stable, even at high temperatures and they can be engineered to incorporate additional favourable properties to target glioblastoma cells with exceptionally high affinity. The new DARPins will be coupled to dextran-coated iron oxide nanoparticles, such as ferucarbotran or nanomag-MIP, which has been used clinically as a contrast agent for Magnetic Resonance Imaging (MRI). These particles are safe to use in patients and are traceable within the body. When stimulated by an appropriate alternating magnetic current, the particles generate heat that can kill cancer cells very effectively. The conjugation of DARPins with ferucarbotran or nanomag-MIP (DARTRIX particle) leads to a potent therapeutic by delivering targeted hyperthermia to glioblastoma. In addition, DARTRIX particle will be created economically, exploiting the fact that DARPins can be produced to GMP in gram quantities using E. coli. The DARTRIX particles will target to glioblastoma cells by virtue of the high affinity and specificity of DARPins and the particles will remain in place when heated. By using DARPins to target the DARTRIX particle to tumour cells before application of the magnetic current, it should be possible to generate toxic heat specifically in the tumour. The consortium has all the skills and knowledge to develop DARPins from bench-to-bedside for glioblastoma treatment. This DARTRIX particle will pioneer targeted hyperthermic cancer treatment of glioblastoma in an innovative adaptive first-in-man trial, using direct injection or convection enhanced delivery to localise the particles to the tumour.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP.2013.1.4-2 | Award Amount: 11.56M | Year: 2013

The NanoMag project is to improve and redefine existing analyzing methods and in some cases, to develop new analyzing methods for magnetic nanostructures. Using improved manufacturing technologies we will synthesize magnetic nanoparticles with specific properties that will be analyzed with a multitude of characterization techniques (focusing on both structural as well as magnetic properties) and bring the experimental results together to obtain a self-consistent picture which describes how structural and magnetic properties are interrelated. This extensive survey will be used to define standard measurements and techniques which are necessary for defining a magnetic nanostructure and quality control. NanoMag brings together Europes and internationally leading experts in; manufacturing of magnetic single-core nanoparticles and magnetic multi-core particles, analyzing and characterization of magnetic nanostructures and national metrology institutes. In the consortium we have gathered partners within research institutes, universities and metrology institutes, all carrying out front end research and developing applications in the field of magnetic nanoparticles.


Kasten A.,University of Rostock | Gruttner C.,Micromod Partikeltechnologie GmbH | Kuhn J.-P.,University of Greifswald | Bader R.,University of Rostock | And 2 more authors.
PLoS ONE | Year: 2014

Magnetic resonance imaging (MRI) using measurement of the transverse relaxation time (R2∗) is to be considered as a promising approach for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. While the relationship between core composition of nanoparticles and their MRI properties is well studied, little is known about possible effects on progenitor cells. This in vitro study aims at comparing two magnetic iron oxide nanoparticle types, single vs. multi-core nanoparticles, regarding their physico-chemical characteristics, effects on cellular behavior of adipose tissue-derived stem cells (ASC) like differentiation and proliferation as well as their detection and quantification by means of MRI. Quantification of both nanoparticle types revealed a linear correlation between labeling concentration and R2∗values. However, according to core composition, different levels of labeling concentrations were needed to achieve comparable R2∗values. Cell viability was not altered for all labeling concentrations, whereas the proliferation rate increased with increasing labeling concentrations. Likewise, deposition of lipid droplets as well as matrix calcification revealed to be highly dose-dependent particularly regarding multi-core nanoparticle-labeled cells. Synthesis of cartilage matrix proteins and mRNA expression of collagen type II was also highly dependent on nanoparticle labeling. In general, the differentiation potential was decreased with increasing labeling concentrations. This in vitro study provides the proof of principle for further in vivo tracking experiments of progenitor cells using nanoparticles with different core compositions but also provides striking evidence that combined testing of biological and MRI properties is advisable as improved MRI properties of multi-core nanoparticles may result in altered cell functions. © 2014 Kasten et al. Source


Eberbeck D.,Physikalisch - Technische Bundesanstalt | Dennis C.L.,U.S. National Institute of Standards and Technology | Huls N.F.,U.S. National Institute of Standards and Technology | Krycka K.L.,U.S. National Institute of Standards and Technology | And 2 more authors.
IEEE Transactions on Magnetics | Year: 2013

Biocompatible magnetic nanoparticles are interesting tracers for diagnostic imaging techniques, including magnetic resonance imaging and magnetic particle imaging (MPI). Here, we will present our studies of the physical and especially magnetic properties of dextran coated multicore magnetic iron oxide nanoparticles, with promising high MPI signals revealed by magnetic particle spectroscopy (MPS) measurements. The Nanomag-MIP particles with a hydrodynamic diameter of 106 nm show an increase of the MPS amplitude by a factor of about two at the 3rd harmonic, as compared to Resovist. In particular, the signal improves progressively with the order of the harmonic, a prerequisite for better spatial resolution. To understand this behavior, we investigated the samples using quasistatic magnetization measurements yielding bimodal size distributions for both systems, and magnetorelaxometry providing the mean effective anisotropy constant. The mean effective magnetic diameter of the dominant larger size mode is 19 nm with a dispersion parameter of σ=0.3 for Nanomag-MIP, and 22 nm with σ=0.25 for Resovist. However, about 80% of the magnetic nanoparticles of Nanomag-MIP belong to this larger size mode whereas in Resovist only 30% do. The remaining Resovist particles are in the range of 5 nm, and, in practice, do not contribute to the MPI signal. © 1965-2012 IEEE. Source

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