Biodegradable Polyphosphoester Micelles Act as Both Background-free 31P Magnetic Resonance Imaging Agents and Drug Nanocarriers

Imaging and tracing materials inside the body is essential to develop functional materials for personalized therapies, including drug delivering nanocarriers and artificial tissues. Magnetic Resonance Imaging (MRI) is a key whole-body imaging technology, where heteronuclear MRI agents enable background-free, quantitative labeling. However, many MRI agents raised concerns due to environmental pollution and organ accumulation. As a solution, we developed a biodegradable, biocompatible polymer platform for heteronuclear 31P magnetic resonance imaging (MRI). We introduce polyphosphoester colloids for heteronuclear MRI using 31P-nucleus. 31P MRI has been severely hampered by unfavorable magnetic resonance properties of 31P, including intrinsic background and low sensitivity. We overcame these fundamental challenges in imaging of 31P by tailoring molecular and structural features of polymeric colloids. We have synthesized gradient-type polyphosphonate copolymers that self-assemble into well-defined micelles. The gradient leads to favorable MRI characteristics compared with homo- and block copolymers. Background-free imaging and biodegradation were proven in vivo in Manduca sexta. Furthermore, we demonstrate by encapsulation of the potent drug PROTAC ARV-825 that these amphiphilic copolymers can simultaneously deliver hydrophobic drugs and thus enable theranostics. We present a unique platform of biocompatible, degradable polyphosphoesters that inherently act as background-free MRI agents and delivery vehicles.