Publications by authors named "Seyed Mohammadali Dadfar"

6 Publications

  • Page 1 of 1

Molecular magnetic resonance imaging of Alpha-v-Beta-3 integrin expression in tumors with ultrasound microbubbles.

Biomaterials 2021 08 27;275:120896. Epub 2021 May 27.

Institute for Experimental Molecular Imaging, RWTH Aachen University, 52074, Aachen, Germany. Electronic address:

Microbubbles (MB) are used as ultrasound (US) contrast agents and can be efficiently targeted against markers of angiogenesis and inflammation. Due to their gas core, MB locally alter susceptibilities in magnetic resonance imaging (MRI), but unfortunately, the resulting contrast is low and not sufficient to generate powerful molecular MRI probes. Therefore, we investigated whether a potent molecular MR agent can be generated by encapsulating superparamagnetic iron oxide nanoparticles (SPION) in the polymeric shell of poly (n-butylcyanoacrylate) (PBCA) MB and targeted them against αβ integrins on the angiogenic vasculature of 4T1 murine breast carcinomas. SPION-MB consist of an air core and a multi-layered polymeric shell enabling efficient entrapment of SPION. The mean size of SPION-MB was 1.61 ± 0.32 μm. Biotin-streptavidin coupling was employed to functionalize the SPION-MB with cyclic RGDfK (Arg-Gly-Asp) and RADfK (Arg-Ala-Asp) peptides. Cells incubated with RGD-SPION-MB showed enhanced transverse relaxation rates compared with SPION-MB and blocking αβ integrin receptors with excess free cRGDfK significantly reduced RGD-SPION-MB binding. Due to the fast binding of RGD-SPION-MB in vivo, dynamic susceptibility contrast MRI was employed to track their retention in tumors in real-time. Higher retention of RGD-SPION-MB was observed compared with SPION-MB and RAD-SPION-MB. To corroborate our MRI results, molecular US was performed the following day using the destruction-replenishment method. Both imaging modalities consistently indicated higher retention of RGD-SPION-MB in angiogenic vessels compared with SPION-MB and RAD-SPION-MB. Competitive blocking experiments in mice further confirmed that the binding of RGD-SPION-MB to αβ integrin receptors is specific. Overall, this study demonstrates that RGD-SPION-MB can be employed as molecular MR/US contrast agents and are capable of assessing the αβ integrin expression in the neovasculature of malignant tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120896DOI Listing
August 2021

Image-derived mean velocity measurement for prediction of coronary flow reserve in a canonical stenosis phantom using magnetic particle imaging.

PLoS One 2021 22;16(4):e0249697. Epub 2021 Apr 22.

Department of Diagnostic and Interventional Radiology, Uniklinikum Aachen, Aachen, Germany.

Introduction: Aim of this study is to evaluate whether magnetic particle imaging (MPI) is capable of measuring velocities occurring in the coronary arteries and to compute coronary flow reserve (CFR) in a canonical phantom as a preliminary study.

Methods: For basic velocity measurements, a circulation phantom was designed containing replaceable glass tubes with three varying inner diameters, matching coronary-vessel diameters. Standardised boluses of superparamagnetic-iron-oxide-nanoparticles were injected and visualised by MPI. Two image-based techniques were competitively applied to calibrate the respective glass tube and to compute the mean velocity: full-duration-at-half-maximum (FDHM) and tracer dilution (TD) method. For CFR-calculation, four necessary settings of the circulation model of a virtual vessel with an inner diameter of 4 mm were generated using differently sized glass tubes and a stenosis model. The respective velocities in stenotic glass tubes were computed without recalibration.

Results: On velocity level, comparison showed a good agreement (rFDHM = 0.869, rTD = 0.796) between techniques, preferably better for 4 mm and 6 mm inner diameter glass tubes. On CFR level MPI-derived CFR-prediction performed considerably inferior with a relative error of 20-44%.

Conclusions: MPI has the ability to reliably measure coronary blood velocities at rest as well as under hyperaemia and therefore may be suitable for CFR calculation. Calibration-associated accuracy of CFR-measurements has to be improved substantially in further studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249697PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061921PMC
April 2021

Influence of Riboflavin Targeting on Tumor Accumulation and Internalization of Peptostar Based Drug Delivery Systems.

Bioconjug Chem 2020 12 25;31(12):2691-2696. Epub 2020 Nov 25.

Institute for Experimental Molecular Imaging, University Hospital Aachen, Forckenbeckstrasse 55, 52074 Aachen, Germany.

Riboflavin carrier protein (RCP) and riboflavin transporters (RFVTs) have been reported to be highly overexpressed in various cancer cells. Hence, targeting RCP and RFVTs using riboflavin may enhance tumor accumulation and internalization of drug delivery systems. To test this hypothesis, butyl-based 3-arm peptostar polymers were synthesized consisting of a lysine core (10 units per arm) and a sarcosine shell (100 units per arm). The end groups of the arms and the core were successfully modified with riboflavin and the Cy5.5 fluorescent dye, respectively. While in phosphate buffered saline the functionalized peptostars showed a bimodal behavior and formed supramolecular structures over time, they were stable in the serum maintaining their hydrodynamic diameter of 12 nm. Moreover, the polymers were biocompatible and the uptake of riboflavin targeted peptostars in A431 and PC3 cells was higher than in nontargeted controls and could be blocked competitively. In vivo, the polymers showed a moderate passive tumor accumulation, which was not significantly different between targeted and nontargeted peptostars. Nonetheless, at the histological level, internalization into tumor cells was strongly enhanced for the riboflavin-targeted peptostars. Based on these results, we conclude that passive accumulation is dominating the accumulation of peptostars, while tumor cell internalization is strongly promoted by riboflavin targeting.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00593DOI Listing
December 2020

Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance.

J Nanobiotechnology 2020 Jan 28;18(1):22. Epub 2020 Jan 28.

Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Forckenbeckstr. 55, 52074, Aachen, Germany.

Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.
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http://dx.doi.org/10.1186/s12951-020-0580-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986086PMC
January 2020

Novel dual-responsive semi-interpenetrating polymer network hydrogels for controlled release of anticancer drugs.

J Biomed Mater Res A 2019 10 22;107(10):2327-2339. Epub 2019 Jun 22.

Faculty of Medicine, Institute for Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany.

Novel dual-responsive hydrogels of semi-interpenetrating polymer networks (semi-IPNs) based on temperature-sensitive N-isopropylacrylamide (NIPAA) and pH-sensitive N-ethylmaleamic acid (NEMA) monomers and sodium alginate polymer were synthesized using free-radical polymerization in the presence of N,N'-methylenebisacrylamide as a crosslinker. Stimuli-responsive properties of the semi-IPN hydrogels showed remarkable sensitivity to both temperature and pH without limitation in NEMA content. Doxorubicin hydrochloride (DOX) as a model drug was efficiently loaded into the hydrogels and the release profiles of drug from them were investigated. The results of in vitro studies showed a quick DOX release in the conditions simulating tumor environment (phosphate-buffered saline [PBS], pH 6.5, 37°C) or endosomes/lysosomes (PBS, pH 5.5, 37°C) compared to simulated human physiological conditions (PBS, pH 7.4, 37°C). In conclusion, the novel poly(NIPAA-co-NEMA) semi-IPN hydrogels could be a promising candidate for targeted and controlled release of anticancer drugs in drug delivery system.
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http://dx.doi.org/10.1002/jbm.a.36741DOI Listing
October 2019

Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications.

Adv Drug Deliv Rev 2019 01 11;138:302-325. Epub 2019 Jan 11.

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Aachen, Germany; Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands; Department of Targeted Therapeutics, University of Twente, Enschede, The Netherlands. Electronic address:

Many different iron oxide nanoparticles have been evaluated over the years, for a wide variety of biomedical applications. We here summarize the synthesis, surface functionalization and characterization of iron oxide nanoparticles, as well as their (pre-) clinical use in diagnostic, therapeutic and theranostic settings. Diagnostic applications include liver, lymph node, inflammation and vascular imaging, employing mostly magnetic resonance imaging but recently also magnetic particle imaging. Therapeutic applications encompass iron supplementation in anemia and advanced cancer treatments, such as modulation of macrophage polarization, magnetic fluid hyperthermia and magnetic drug targeting. Because of their properties, iron oxide nanoparticles are particularly useful for theranostic purposes. Examples of such setups, in which diagnosis and therapy are intimately combined and in which iron oxide nanoparticles are used, are image-guided drug delivery, image-guided and microbubble-mediated opening of the blood-brain barrier, and theranostic tissue engineering. Together, these directions highlight the versatility and the broad applicability of iron oxide nanoparticles, and indicate the integration in future medical practice of multiple iron oxide nanoparticle-based materials.
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http://dx.doi.org/10.1016/j.addr.2019.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115878PMC
January 2019
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