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 () and Frederik R. Wurm ()
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Olga Koshkina: University of Twente
Timo Rheinberger: University of Twente
Vera Flocke: Heinrich Heine University
Anton Windfelder: Fraunhofer Institute for Molecular Biology and Applied Ecology IME
Pascal Bouvain: Heinrich Heine University
Naomi M. Hamelmann: University of Twente
Jos M. J. Paulusse: University of Twente
Hubert Gojzewski: University of Twente
Ulrich Flögel: Heinrich Heine University
Frederik R. Wurm: University of Twente

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40089-0

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