Theranostic Trigger-Responsive Carbon Monoxide-Generating Microbubbles.

carbon monoxide therapy cardiovascular disease microbubbles poly-n-butyl-cyanoacrylate (PBCA) ultrasound

Journal

Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338

Informations de publication

Date de publication:
05 2022
Historique:
revised: 04 03 2022
received: 11 02 2022
pubmed: 2 4 2022
medline: 7 5 2022
entrez: 1 4 2022
Statut: ppublish

Résumé

Carbon monoxide (CO) is a gaseous signaling molecule that modulates inflammation, cell survival, and recovery after myocardial infarction. However, handling and dosing of CO as a compressed gas are difficult. Here, light-triggerable and magnetic resonance imaging (MRI)-detectable CO release from dimanganese decacarbonyl (CORM-1) are demonstrated, and the development of CORM-1-loaded polymeric microbubbles (COMB) is described as an ultrasound (US)- and MRI-imageable drug delivery platform for triggerable and targeted CO therapy. COMB are synthesized via a straightforward one-step loading protocol, present a narrow size distribution peaking at 2 µm, and show excellent performance as a CORM-1 carrier and US contrast agent. Light irradiation of COMB induces local production and release of CO, as well as enhanced longitudinal and transversal relaxation rates, enabling MRI monitoring of CO delivery. Proof-of-concept studies for COMB-enabled light-triggered CO release show saturation of hemoglobin with CO in human blood, anti-inflammatory differentiation of macrophages, reduction of hypoxia-induced reactive oxygen species (ROS) production, and inhibition of ischemia-induced apoptosis in endothelial cells and cardiomyocytes. These findings indicate that CO-generating MB are interesting theranostic tools for attenuating hypoxia-associated and ROS-mediated cell and tissue damage in cardiovascular disease.

Identifiants

pubmed: 35363403
doi: 10.1002/smll.202200924
doi:

Substances chimiques

Organometallic Compounds 0
Reactive Oxygen Species 0
Carbon Monoxide 7U1EE4V452

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2200924

Subventions

Organisme : European Research Council
ID : 864 121
Pays : International

Informations de copyright

© 2022 The Authors. Small published by Wiley-VCH GmbH.

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Auteurs

Vertika Pathak (V)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Karolin Roemhild (K)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.
Institute of Pathology, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Sandra Schipper (S)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.
Department of General, Visceral and Transplantation Surgery, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Nicolas Groß-Weege (N)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Teresa Nolte (T)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Stephan Ruetten (S)

Electron Microscopy, Institute of Pathology, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Eva Miriam Buhl (EM)

Electron Microscopy, Institute of Pathology, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Asmaa El Shafei (A)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Marek Weiler (M)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Lukas Martin (L)

Department of Intensive Care Medicine, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Gernot Marx (G)

Department of Intensive Care Medicine, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Volkmar Schulz (V)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Fabian Kiessling (F)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

Twan Lammers (T)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.
Department of Pharmaceutics, Utrecht University, Utrecht, 3584CG, The Netherlands.
Department of Targeted Therapeutics, University of Twente, Enschede, 7522 NB, The Netherlands.

Patrick Koczera (P)

Institute for Experimental Molecular Imaging, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.
Department of Intensive Care Medicine, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Clinic, 52074, Aachen, Germany.

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