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Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

View ORCID ProfileDeniz A. Bölükbas, Stefan Datz, Charlotte Meyer-Schwickerath, Carmela Morrone, Ali Doryab, Dorothee Gößl, Malamati Vreka, Lin Yang, Christian Argyo, Sabine H. van Rijt, Michael Lindner, Oliver Eickelberg, Tobias Stoeger, Otmar Schmid, Sandra Lindstedt, Georgios T. Stathopoulos, Thomas Bein, Darcy E. Wagner, Silke Meiners
doi: https://doi.org/10.1101/2020.03.05.969212
Deniz A. Bölükbas
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
2Lung Bioengineering and Regeneration, Dept of Experimental Medical Sciences, Stem Cell Centre, Wallenberg Center for Molecular Medicine, Lund University Cancer Centre (LUCC), Lund University, 22362 Lund, Sweden
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  • ORCID record for Deniz A. Bölükbas
Stefan Datz
3Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany
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Charlotte Meyer-Schwickerath
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Carmela Morrone
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Ali Doryab
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Dorothee Gößl
3Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany
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Malamati Vreka
4Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, 26504 Patras, Greece
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Lin Yang
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Christian Argyo
3Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany
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Sabine H. van Rijt
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Michael Lindner
5Center of Thoracic Surgery Munich, Asklepios Clinic Munich-Gauting, and Asklepios Biobank for Diseases of the Lung, Comprehensive Pneumology Center (CPC), Ludwig-Maximilians University and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), 82131 Gauting, Germany
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Oliver Eickelberg
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Tobias Stoeger
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Otmar Schmid
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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Sandra Lindstedt
6Dept of Cardiothoracic Surgery, Heart and Lung Transplantation, Lund University Hospital 22242 Lund, Sweden
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Georgios T. Stathopoulos
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
4Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, 26504 Patras, Greece
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Thomas Bein
3Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany
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Darcy E. Wagner
2Lung Bioengineering and Regeneration, Dept of Experimental Medical Sciences, Stem Cell Centre, Wallenberg Center for Molecular Medicine, Lund University Cancer Centre (LUCC), Lund University, 22362 Lund, Sweden
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  • For correspondence: darcy.wagner@med.lu.se silke.meiners@helmholtz-muenchen.de
Silke Meiners
1Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
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  • For correspondence: darcy.wagner@med.lu.se silke.meiners@helmholtz-muenchen.de
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Abstract

Nanomedicines hold immense promise for a number of devastating diseases due to the ability to custom-design both the carrier and cargo. However, their clinical implementation has been hampered by physicochemical and biological barriers and off-target deposition which impair cell specific targeting, especially in internal organs. This study reports a new delivery approach using organ-restricted vascular delivery to allow for direct administration and recirculation of stimuli-responsive nanoparticles to promote cellular uptake into an organ of interest. Using this technique, nanoparticles reach the interior of dense tumors and are selectively taken up by lung cancer cells. Importantly, this surgical approach is essential as the same nanoparticles do not reach lung tumor cells upon systemic or intratracheal administration. Organ-restricted vascular delivery thus opens up new avenues for optimized nanotherapies for cancer and other diseases.

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Posted March 06, 2020.
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Organ-restricted vascular delivery of nanoparticles for lung cancer therapy
Deniz A. Bölükbas, Stefan Datz, Charlotte Meyer-Schwickerath, Carmela Morrone, Ali Doryab, Dorothee Gößl, Malamati Vreka, Lin Yang, Christian Argyo, Sabine H. van Rijt, Michael Lindner, Oliver Eickelberg, Tobias Stoeger, Otmar Schmid, Sandra Lindstedt, Georgios T. Stathopoulos, Thomas Bein, Darcy E. Wagner, Silke Meiners
bioRxiv 2020.03.05.969212; doi: https://doi.org/10.1101/2020.03.05.969212
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Organ-restricted vascular delivery of nanoparticles for lung cancer therapy
Deniz A. Bölükbas, Stefan Datz, Charlotte Meyer-Schwickerath, Carmela Morrone, Ali Doryab, Dorothee Gößl, Malamati Vreka, Lin Yang, Christian Argyo, Sabine H. van Rijt, Michael Lindner, Oliver Eickelberg, Tobias Stoeger, Otmar Schmid, Sandra Lindstedt, Georgios T. Stathopoulos, Thomas Bein, Darcy E. Wagner, Silke Meiners
bioRxiv 2020.03.05.969212; doi: https://doi.org/10.1101/2020.03.05.969212

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