Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety
Harald Unterweger,1,* Christina Janko,1,* Tamara Folk,1 Iwona Cicha,1 Noémi Kovács,2 Gyula Gyebnár,3 Ildikó Horváth,4 Domokos Máthé,2,3 Kang H Zheng,5 Bram F Coolen,6 Erik Stroes,5 János Szebeni,7,8 Christoph Alexiou,1 László Dézsi,7,8,* Stefan Lyer1,* 1ENT-Department...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-04-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/comparative-in-vitro-and-in-vivo-evaluation-of-different-iron-oxide-ba-peer-reviewed-fulltext-article-IJN |
| _version_ | 1797840631531307008 |
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| author | Unterweger H Janko C Folk T Cicha I Kovács N Gyebnár G Horváth I Máthé D Zheng KH Coolen BF Stroes E Szebeni J Alexiou C Dézsi L Lyer S |
| author_facet | Unterweger H Janko C Folk T Cicha I Kovács N Gyebnár G Horváth I Máthé D Zheng KH Coolen BF Stroes E Szebeni J Alexiou C Dézsi L Lyer S |
| author_sort | Unterweger H |
| collection | DOAJ |
| description | Harald Unterweger,1,* Christina Janko,1,* Tamara Folk,1 Iwona Cicha,1 Noémi Kovács,2 Gyula Gyebnár,3 Ildikó Horváth,4 Domokos Máthé,2,3 Kang H Zheng,5 Bram F Coolen,6 Erik Stroes,5 János Szebeni,7,8 Christoph Alexiou,1 László Dézsi,7,8,* Stefan Lyer1,* 1ENT-Department, Section of Experimental Oncology und Nanomedicine (SEON), Universitätsklinikum Erlangen, Erlangen, Germany; 2Hungarian Centre of Excellence for Molecular Medicine, Semmelweis University, Budapest, Hungary; 3Medical Imaging Centre, Semmelweis University, Budapest, Hungary; 4Department Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary; 5Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, the Netherlands; 6Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, the Netherlands; 7Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; 8SeroScience Ltd, Budapest, Hungary*These authors contributed equally to this workCorrespondence: Harald Unterweger, Universitätsklinikum Erlangen, Glueckstr. 10a, Erlangen, 91054, Germany, Tel +49 9131 85-33142, Fax +49 9131 85-34828, Email harald.unterweger@uk-erlangen.deIntroduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects.Methods: Following the development of a potent iron oxide-based contrast agent SPIONDex, we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats.Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPIONDex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPIONDex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPIONDex.Conclusion: The results indicate that SPIONDex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation.Keywords: magnetic resonance imaging, MRI, nanomedicine, nanoparticles, complement activation, CARPA |
| first_indexed | 2024-04-09T16:17:58Z |
| format | Article |
| id | doaj.art-436cf383b187403abd366d9c5800a7fe |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-09T16:17:58Z |
| publishDate | 2023-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-436cf383b187403abd366d9c5800a7fe2023-04-23T18:44:07ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-04-01Volume 182071208683218Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient SafetyUnterweger HJanko CFolk TCicha IKovács NGyebnár GHorváth IMáthé DZheng KHCoolen BFStroes ESzebeni JAlexiou CDézsi LLyer SHarald Unterweger,1,* Christina Janko,1,* Tamara Folk,1 Iwona Cicha,1 Noémi Kovács,2 Gyula Gyebnár,3 Ildikó Horváth,4 Domokos Máthé,2,3 Kang H Zheng,5 Bram F Coolen,6 Erik Stroes,5 János Szebeni,7,8 Christoph Alexiou,1 László Dézsi,7,8,* Stefan Lyer1,* 1ENT-Department, Section of Experimental Oncology und Nanomedicine (SEON), Universitätsklinikum Erlangen, Erlangen, Germany; 2Hungarian Centre of Excellence for Molecular Medicine, Semmelweis University, Budapest, Hungary; 3Medical Imaging Centre, Semmelweis University, Budapest, Hungary; 4Department Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary; 5Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, the Netherlands; 6Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, the Netherlands; 7Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; 8SeroScience Ltd, Budapest, Hungary*These authors contributed equally to this workCorrespondence: Harald Unterweger, Universitätsklinikum Erlangen, Glueckstr. 10a, Erlangen, 91054, Germany, Tel +49 9131 85-33142, Fax +49 9131 85-34828, Email harald.unterweger@uk-erlangen.deIntroduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects.Methods: Following the development of a potent iron oxide-based contrast agent SPIONDex, we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats.Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPIONDex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPIONDex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPIONDex.Conclusion: The results indicate that SPIONDex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation.Keywords: magnetic resonance imaging, MRI, nanomedicine, nanoparticles, complement activation, CARPAhttps://www.dovepress.com/comparative-in-vitro-and-in-vivo-evaluation-of-different-iron-oxide-ba-peer-reviewed-fulltext-article-IJNmagnetic resonance imagingmrinanomedicinenanoparticlescomplement activationcarpa |
| spellingShingle | Unterweger H Janko C Folk T Cicha I Kovács N Gyebnár G Horváth I Máthé D Zheng KH Coolen BF Stroes E Szebeni J Alexiou C Dézsi L Lyer S Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety International Journal of Nanomedicine magnetic resonance imaging mri nanomedicine nanoparticles complement activation carpa |
| title | Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety |
| title_full | Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety |
| title_fullStr | Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety |
| title_full_unstemmed | Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety |
| title_short | Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety |
| title_sort | comparative in vitro and in vivo evaluation of different iron oxide based contrast agents to promote clinical translation in compliance with patient safety |
| topic | magnetic resonance imaging mri nanomedicine nanoparticles complement activation carpa |
| url | https://www.dovepress.com/comparative-in-vitro-and-in-vivo-evaluation-of-different-iron-oxide-ba-peer-reviewed-fulltext-article-IJN |
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