Optical imaging of the whole-body to cellular biodistribution of clinical-stage PEG-b-pHPMA-based core-crosslinked polymeric micelles.

Animals Cell Line, Tumor Mice Micelles Optical Imaging Polymers Tissue Distribution X-Ray Microtomography

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 12 2020
Historique:
received: 11 08 2020
revised: 25 09 2020
accepted: 26 09 2020
pubmed: 4 10 2020
medline: 22 6 2021
entrez: 3 10 2020
Statut: ppublish

Résumé

Core-crosslinked polymeric micelles (CCPM) based on PEG-b-pHPMA-lactate are clinically evaluated for the treatment of cancer. We macroscopically and microscopically investigated the biodistribution and target site accumulation of CCPM. To this end, fluorophore-labeled CCPM were intravenously injected in mice bearing 4T1 triple-negative breast cancer (TNBC) tumors, and their localization at the whole-body, tissue and cellular level was analyzed using multimodal and multiscale optical imaging. At the organism level, we performed non-invasive 3D micro-computed tomography-fluorescence tomography (μCT-FLT) and 2D fluorescence reflectance imaging (FRI). At the tissue and cellular level, we performed extensive immunohistochemistry, focusing primarily on cancer, endothelial and phagocytic immune cells. The CCPM achieved highly efficient tumor targeting in the 4T1 TNBC mouse model (18.6 %ID/g), with values twice as high as those in liver and spleen (9.1 and 8.9 %ID/g, respectively). Microscopic analysis of tissue slices revealed that at 48 h post injection, 67% of intratumoral CCPM were localized extracellularly. Phenotypic analyses on the remaining 33% of intracellularly accumulated CCPM showed that predominantly F4/80

Identifiants

DOI: 10.1016/j.jconrel.2020.09.046 PMID: 33010332 PMC: PMC7611891
pubmed: 33010332
pii: S0168-3659(20)30562-9
doi: 10.1016/j.jconrel.2020.09.046
pmc: PMC7611891
mid: EMS137160
pii:
doi:

Substances chimiques

Micelles 0
Polymers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

805-816

Subventions

Organisme : European Research Council
ID : 864121
Pays : International

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

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Auteurs

Ilaria Biancacci (I)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Qingxue Sun (Q)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Diana Möckel (D)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; Gremse-IT GmbH, Aachen, Germany.

Felix Gremse (F)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; Gremse-IT GmbH, Aachen, Germany.

Stefanie Rosenhain (S)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; Gremse-IT GmbH, Aachen, Germany.

Fabian Kiessling (F)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Matthias Bartneck (M)

Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.

Qizhi Hu (Q)

Cristal Therapeutics, Maastricht, the Netherlands.

Marielle Thewissen (M)

Cristal Therapeutics, Maastricht, the Netherlands.

Gert Storm (G)

Department of Pharmaceutics, Utrecht University, Utrecht, the Netherlands; Department of Targeted Therapeutics, University of Twente, Enschede, the Netherlands; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Wim E Hennink (WE)

Department of Pharmaceutics, Utrecht University, Utrecht, the Netherlands.

Yang Shi (Y)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Cristianne J F Rijcken (CJF)

Cristal Therapeutics, Maastricht, the Netherlands. Electronic address: cristianne.rijcken@cristaltherapeutics.com.

Twan Lammers (T)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; Department of Pharmaceutics, Utrecht University, Utrecht, the Netherlands; Department of Targeted Therapeutics, University of Twente, Enschede, the Netherlands. Electronic address: tlammers@ukaachen.de.

Alexandros Marios Sofias (AM)

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany. Electronic address: asofias@ukaachen.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Préparations pharmaceutiques › Micelles › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Techniques d'investigation › Imagerie optique › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Pharmacocinétique › Distribution tissulaire › Optical imaging of the whole-body to cellular...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Tomographie à rayons X › Tomodensitométrie › Microtomographie aux rayons X › Optical imaging of the whole-body to cellular...