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Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors

B. Theek, M. Baues, F. Gremse, R. Pola, M. Pechar, I. Negwer, K. Koynov, B. Weber, M. Barz, W. Jahnen-Dechent, G. Storm, F. Kiessling, T. Lammers,

. 2018 ; 282 (-) : 25-34. [pub] 20180504

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19035266

Grantová podpora
309495 European Research Council - International

Tumors are characterized by leaky blood vessels, and by an abnormal and heterogeneous vascular network. These pathophysiological characteristics contribute to the enhanced permeability and retention (EPR) effect, which is one of the key rationales for developing tumor-targeted drug delivery systems. Vessel abnormality and heterogeneity, however, which typically result from excessive pro-angiogenic signaling, can also hinder efficient drug delivery to and into tumors. Using histidine-rich glycoprotein (HRG) knockout and wild type mice, and HRG-overexpressing and normal t241 fibrosarcoma cells, we evaluated the effect of genetically induced and macrophage-mediated vascular normalization on the tumor accumulation and penetration of 10-20 nm-sized polymeric drug carriers based on poly(N-(2-hydroxypropyl)methacrylamide). Multimodal and multiscale optical imaging was employed to show that normalizing the tumor vasculature improves the accumulation of fluorophore-labeled polymers in tumors, and promotes their penetration out of tumor blood vessels deep into the interstitium.

Citace poskytuje Crossref.org

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$a Tumors are characterized by leaky blood vessels, and by an abnormal and heterogeneous vascular network. These pathophysiological characteristics contribute to the enhanced permeability and retention (EPR) effect, which is one of the key rationales for developing tumor-targeted drug delivery systems. Vessel abnormality and heterogeneity, however, which typically result from excessive pro-angiogenic signaling, can also hinder efficient drug delivery to and into tumors. Using histidine-rich glycoprotein (HRG) knockout and wild type mice, and HRG-overexpressing and normal t241 fibrosarcoma cells, we evaluated the effect of genetically induced and macrophage-mediated vascular normalization on the tumor accumulation and penetration of 10-20 nm-sized polymeric drug carriers based on poly(N-(2-hydroxypropyl)methacrylamide). Multimodal and multiscale optical imaging was employed to show that normalizing the tumor vasculature improves the accumulation of fluorophore-labeled polymers in tumors, and promotes their penetration out of tumor blood vessels deep into the interstitium.
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$a Baues, Maike $u Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Aachen, Germany.
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$a Gremse, Felix $u Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Aachen, Germany.
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$a Pola, Robert $u Institute of Macromolecular Chemistry, Czech Academy of Science, Prague, Czech Republic.
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$a Pechar, Michal $u Institute of Macromolecular Chemistry, Czech Academy of Science, Prague, Czech Republic.
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$a Negwer, Inka $u Max Planck Institute for Polymer Research, Mainz, Germany.
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$a Koynov, Kaloian $u Max Planck Institute for Polymer Research, Mainz, Germany.
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$a Weber, Benjamin $u Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany.
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$a Storm, Gert $u Department of Targeted Therapeutics, Biomaterial Science and Technology, University of Twente, Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
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$a Kiessling, Fabian $u Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Aachen, Germany.
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$a Lammers, Twan $u Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic and Helmholtz Institute for Biomedical Engineering, Aachen, Germany; Department of Targeted Therapeutics, Biomaterial Science and Technology, University of Twente, Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. Electronic address: tlammers@ukaachen.de.
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