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

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.

Nano-PROTACs: state of the art and perspectives

“…In addition, polymeric nanoparticles are simple to prepare, have adjustable physicochemical properties, and can be used to deliver a wide variety of drugs such as small molecules, biological macromolecules, proteins, and nucleic acids. Despite all the advantages mentioned above, studies on polymer nanoparticle-based PROTAC drugs 61,68–75 are currently facing serious drawbacks for efficient encapsulation of PROTACs, smart delivery systems, and clinical translation. To solve these dilemmas, Liu et al 73 used two synthetic polymers, DSPE-PEG and PDSA, to prepare a biodegradable polymer nanoparticle for BRD4 degrader ARV-771 delivery (Fig.…”

Nanomaterial-Based Drug Delivery Systems for Pain Treatment and Relief: From the Delivery of a Single Drug to Co-Delivery of Multiple Therapeutics

“…Nanocarriers can improve therapeutic effects and treat diseases with minimal side effects by improving drug stability, reducing adverse reactions, controlling release efficiency, and changing pharmacokinetic characteristics [ 6 ]. Additionally, nanotechnology-enabled tools can enhance medical imaging techniques by providing better contrast agents and improved resolution [ 7 , 8 ]. Nanosensors and nanodevices allow for the real-time monitoring of various parameters within the body, providing valuable data for diagnosing and managing diseases [ 9 ].…”