Bio-responsive polymers for dual 31P/19F-magnetic resonance to detect reactive oxygen species in vivo

Abstract

Biocompatible metal-free agents are emerging as a promising alternative to commercial magnetic resonance (MR) contrast agents, but there is an additional need for novel probes with enhanced responsiveness in preclinical MR testing to effectively target diverse pathological conditions. To address this, we develop hydrophilic phospho-/fluoropolymers as dual MR probes. Incorporating thiophosphoester groups (P = S) into the polymer structure produces a distinct chemical shift (~59 ppm) in phosphorus MR (31P-MR), reducing biological signals interference. Reactive oxygen species (ROS) oxidize the P = S groups, causing a detectable shift in 31P-MR, enabling precise localization of ROS, abundant in inflammation and cancer. To enhance this capability, bioinert trifluoromethyl groups (CF3) are added, creating a “hotspot” for fluorine MR (19F-MR), aiding in vivo localization. Both in vitro and in vivo testing demonstrate the probe’s high specificity and responsiveness, underscoring its potential as a sensitive ROS sensor and dual MR-traceable tool in cancer research. Magnetic resonance imaging lack biocompatible metal-free contrast agents with specific functionality. Here, hydrophilic phospho-/fluoropolymers are developed as 31P/ 19 F-MR probes for in vivo detection of reactive oxygen species.