Biodegradable polyphosphoester micelles act as both background-free 31P magnetic resonance imaging agents and drug nanocarriers

Olga Koshkina; Timo Rheinberger; Vera Flocke; Anton Windfelder; Pascal Bouvain; Naomi M Hamelmann; Jos M J Paulusse; Hubert Gojzewski; Ulrich Flögel; Frederik R Wurm

doi:10.1038/s41467-023-40089-0

Biodegradable polyphosphoester micelles act as both background-free ³¹P magnetic resonance imaging agents and drug nanocarriers

Nat Commun. 2023 Jul 19;14(1):4351. doi: 10.1038/s41467-023-40089-0.

Authors

Affiliations

¹ Sustainable Polymer Chemistry Group, Department of Molecules and Materials, MESA+ Institute of Nanotechnology, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands. o.koshkina@utwente.nl.
² Sustainable Polymer Chemistry Group, Department of Molecules and Materials, MESA+ Institute of Nanotechnology, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
³ Department of Molecular Cardiology, Experimental Cardiovascular Imaging, Heinrich Heine University, Düsseldorf, Germany.
⁴ Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Giessen, Germany.
⁵ Laboratory of Experimental Radiology, Justus Liebig University, Giessen, Germany.
⁶ Biomolecular Nanotechnology Group, Department of Molecules and Materials, MESA+ Institute of Nanotechnology, University of Twente, Enschede, The Netherlands.
⁷ Department of Molecular Cardiology, Experimental Cardiovascular Imaging, Heinrich Heine University, Düsseldorf, Germany. floegel@uni-duesseldorf.de.
⁸ Sustainable Polymer Chemistry Group, Department of Molecules and Materials, MESA+ Institute of Nanotechnology, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands. frederik.wurm@utwente.nl.

^# Contributed equally.

Abstract

In vivo monitoring of polymers is crucial for drug delivery and tissue regeneration. Magnetic resonance imaging (MRI) is a whole-body imaging technique, and heteronuclear MRI allows quantitative imaging. However, MRI agents can result in environmental pollution and organ accumulation. To address this, we introduce biocompatible and biodegradable polyphosphoesters, as MRI-traceable polymers using the ³¹P centers in the polymer backbone. We overcome challenges in ³¹P MRI, including background interference and low sensitivity, by modifying the molecular environment of ³¹P, assembling polymers into colloids, and tailoring the polymers' microstructure to adjust MRI-relaxation times. Specifically, gradient-type polyphosphonate-copolymers demonstrate improved MRI-relaxation times compared to homo- and block copolymers, making them suitable for imaging. We validate background-free imaging and biodegradation in vivo using Manduca sexta. Furthermore, encapsulating the potent drug PROTAC allows using these amphiphilic copolymers to simultaneously deliver drugs, enabling theranostics. This first report paves the way for polyphosphoesters as background-free MRI-traceable polymers for theranostic applications.

Publication types

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

MeSH terms

Drug Carriers / chemistry
Drug Delivery Systems / methods
Magnetic Resonance Imaging
Micelles*
Polymers* / chemistry

Substances

Micelles
Polymers
Drug Carriers