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Ultrasound contrast agents are clinically used for diagnosis of internal organs, but ultrasound contrast agents are rarely applied clinically in musculoskeletal disorders. Our study aims to comparatively analyze the differences between ultrasonographic images through peri-injury injection of the clinically used microbubble and researched nanoparticle contrast agents in various muscular injury models. To compare contrast-enhanced images in different muscle injury models, we prepared groups of rats with sham, laceration, punch, contusion, and toxin injection injuries. We measured H2O2 levels using the Amplex Red assay by extracting tissue from the damaged area. As comparative contrast agents, SonoVue®, a commercially available microbubble contrast agent, and poly(vanillinoxalte) (PVO) nanoparticles, which are H2O2-responsive nanoparticles, were used. The difference in contrast between the two contrast agents was recorded as an ultrasound movie, and J-image software 1.53p was used to quantify and analyze the maximum and minimum echogenicity values of the images after contrast enhancement. In the Amplex red assay for the highest H2O2 level in each muscle injury model, the maximum level showed 24 h after the modeling. In the sham rats, PVO injection showed no increased echogenicity except at the needle insertion site, but SonoVue® injection showed increased echo signal throughout the injected muscle immediately after injection. One day after the preparation of the lesion, PVO and SonoVue® were injected into the lesion site and ultrasound was performed on the lesion site. After the injection of PVO nanoparticles, contrast enhancement was observed at the lesion site immediately. SonoVue® injections, on the other hand, showed a widespread pattern of echo signals and an increase in echo retention only at the lesion site over time, but this was not clear. There were statistically significant differences between the highest and lowest echogenicity in PVO and SonoVue® contrast-enhanced images in all models. Contrast enhancement lasted more than 3 h in the PVO injection, but disappeared within 3 h in the SonoVue® injection. PVO nanoparticles showed the possibility of physiologic contrast by CO2 generated by conjugation with H2O2 generated by muscle injuries, and SonoVue® injection observed the possibility of microbubble contrast as a contrast agent with a pooling effect that lasts longer on the lesion. Further research is needed to investigate the use of various ultrasound contrast agents, including nanoparticles, in musculoskeletal disorders, as well as the potential for further utilities of microbubble contrast agents. [ABSTRACT FROM AUTHOR]

Abstract Curcumin is a major active phenolic component of turmeric and has gained great attention in pharmaceutics due to its potent antioxidant, anti-inflammatory and anticancer activity. Here, we developed poly(oxalate- co -curcumin) (POC) as a hydrogen peroxide (H 2 O 2)-activatable polymeric prodrug of curcumin by incorporating curcumin in the backbone of H 2 O 2 -responsive polyoxalate. POC particles effectively scavenged H 2 O 2 and released curcumin in a H 2 O 2 -triggered manner. POC particles exhibited excellent antioxidant and anti-inflammatory activity in activated cells. POC particles intravenously administrated into acetaminophen-intoxicated mice remarkably suppressed the level of alanine transaminase and inhibited apoptotic cell death in liver. Interestingly, POC particles could also enhance the ultrasound contrast in the intoxicated liver due to CO 2 bubble generation through H 2 O 2 -triggered oxidation of peroxalate esters. Given their H 2 O 2 -responsiveness and highly potent antioxidant activity, POC particles hold great translational potential as theranostic agents for H 2 O 2 -associated diseases. Graphical Abstract Poly(oxalate- co -curcumin) (POC) is a hydrogen peroxide (H 2 O 2)-activatable polymeric prodrug of curcumin which incorporates curcumin in the backbone of H 2 O 2 -responsive polyoxalate. POC particles remarkably suppress the level of alanine transaminase and inhibit apoptotic cell death in liver of acetaminophen-intoxicated mice. POC particles also enhance the ultrasound contrast in the intoxicated liver due to CO 2 bubble generation through H 2 O 2 -triggered oxidation of peroxalate esters. Given their H 2 O 2 -responsiveness and highly potent antioxidant activity, POC particles hold great translational potential as theranostic agents for H 2 O 2 -associated diseases. Unlabelled Image [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (IR) injury is an inevitable pathological event occurring when blood is resupplied to the tissues after a period of ischemia. One of major causes of IR injury is the overproduction of reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2), which mediates the expression of various inflammatory cytokines to exacerbate tissue damages. The overproduced H 2 O 2 could therefore serve as a diagnostic and therapeutic biomarker of IR injury. In this study, poly(boronated methacrylate) (pBMA) nanoparticles were developed as nanotheranostic agents for renal IR injury, which not only generate CO 2 bubbles to enhance the ultrasound contrast but also provide potent preventive effects in a H 2 O 2 -triggered manner. The surface of pBMA nanoparticles was decorated with taurodeoxycholic acid (TUDCA) that binds P-selectin overexpressed in inflamed tissues. In the mouse model of renal IR injury, TUDCA-coated pBMA (T-pBMA) nanoparticles preferentially accumulated in the injured kidney and markedly enhanced the ultrasound contrast. T-pBMA nanoparticles also effectively prevented renal IR injury by scavenging H 2 O 2 and suppressing the expression of inflammatory cytokines. Treatment progress of IR injury could be also monitored by echogenic T-pBMA nanoparticles. Given their targeting ability, excellent H 2 O 2 -responsiveness, anti-inflammatory activity and H 2 O 2 -triggered echogenicity, T-pBMA nanoparticles have excellent translational potential for the management of various H 2 O 2 -related diseases including IR injury. [Display omitted] [ABSTRACT FROM AUTHOR]