Synthesis and Characterization of Tissue Plasminogen Activator—Functionalized Superparamagnetic Iron Oxide Nanoparticles for Targeted Fibrin Clot Dissolution
| Autor: | Heid, Susanne, Unterweger, Harald, Tietze, Rainer, Friedrich, Ralf P., Weigel, Bianca, Cicha, Iwona, Eberbeck, Dietmar, Boccaccini, Aldo R., Alexiou, Christoph, Lyer, Stefan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Drug Carriers
tissue plasminogen activator Dose-Response Relationship Drug Endothelial Cells superparamagnetic iron oxide nanoparticles Dextrans drug targeting protein binding Hydrogen-Ion Concentration Ferric Compounds Article lcsh:Chemistry Fibrinolytic Agents lcsh:Biology (General) lcsh:QD1-999 Medizinische Fakultät Spectroscopy Fourier Transform Infrared Humans fibrinolysis ddc:610 Particle Size Magnetite Nanoparticles lcsh:QH301-705.5 activated ester reaction |
| Zdroj: | International Journal of Molecular Sciences, Vol 18, Iss 9, p 1837 (2017) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted great attention in many biomedical fields and are used in preclinical/experimental drug delivery, hyperthermia and medical imaging. In this study, biocompatible magnetite drug carriers, stabilized by a dextran shell, were developed to carry tissue plasminogen activator (tPA) for targeted thrombolysis under an external magnetic field. Different concentrations of active tPA were immobilized on carboxylated nanoparticles through carbodiimide-mediated amide bond formation. Evidence for successful functionalization of SPIONs with carboxyl groups was shown by Fourier transform infrared spectroscopy. Surface properties after tPA immobilization were altered as demonstrated by dynamic light scattering and ζ potential measurements. The enzyme activity of SPION-bound tPA was determined by digestion of fibrin-containing agarose gels and corresponded to about 74% of free tPA activity. Particles were stored for three weeks before a slight decrease in activity was observed. tPA-loaded SPIONs were navigated into thrombus-mimicking gels by external magnets, proving effective drug targeting without losing the protein. Furthermore, all synthesized types of nanoparticles were well tolerated in cell culture experiments with human umbilical vein endothelial cells, indicating their potential utility for future therapeutic applications in thromboembolic diseases. |
| Databáze: | OpenAIRE |
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