Diagnosis and Simultaneous Treatment of Musculoskeletal Injury Using H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles in a Rat Model of Contusion Injury

Ultrasound is clinically used for diagnosis and interventions for musculoskeletal injuries like muscle contusion, but contrast of ultrasonography still remains a challenge in the field of the musculoskeletal system. A level of hydrogen peroxide (H2O2) is known to be elevated during mechanical tissue damage and therefore H2O2 can be exploited as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillin-oxalate) (PVO) as an inflammation-responsive polymeric prodrug of vanillin, which is designed to rapidly respond to H2O2 and exert antioxidant and anti-inflammatory activities. The primary aim of this study is to verify whether PVO nanoparticles could serve as contrast agents as well as therapeutic agents for musculoskeletal injuries simultaneously. In a rat model of contusion-induced muscle injury, PVO nanoparticles generated CO2 bubbles to enhance the ultrasound contrast in the injury site. A single intramuscular injection of PVO nanoparticles also suppressed contusion-induced muscle damages by inhibiting the expression of pro-inflammatory cytokines and inflammatory cell infiltration. We, therefore, anticipate that PVO nanoparticles have great translational potential as not only ultrasound imaging agents but also therapeutic agents for the musculoskeletal disorders such as contusion.