Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles

Abstract

Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated diseases. Based on the notion that PVAX nanoparticles generate CO2 bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H2O2. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H2O2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.

Reactive Oxygen Species Responsive Polymers for Drug Delivery Systems

“…Aryl oxalates may react with H 2 O 2 to form 1,2-dioxetanediones, which can be rapidly converted into carbon dioxide (CO 2 ) and phenols. Thus, aryl oxalate ester bonds in polymerized nanoparticles may induce degradation and then release the payload when exposed to H 2 O 2 to achieve intelligent delivery of drugs (Kim et al, 2017).…”

Applications of Nanobiomaterials in the Therapy and Imaging of Acute Liver Failure

“…Because of easy detection, low cost and no radiation hazard, it has been used as a screening method for liver disease. Conventional ultrasound contrast agents are microbubbles composed of a shell material of lipids and proteins and a gas core, whose diameter is 1-8 μm [209][210][211]. However, there exist undesired imaging https://doi.org/10.1007/s40820-020-00550-x © The authors defects, such as poor blood vessel stability, short echo persistence, and difficulty in penetrating surrounding tissues [212].…”

“…Analogous to ketalized maltodextrin nanoparticles, hydrogen peroxide-activatable peroxalate polymer can produce CO 2 in a H 2 O 2 -induced manner. It was reported that the peroxalate polymers could act as both the ultrasound imaging agent for H 2 O 2 -related inflammatory diseases [ 210 , 211 ], and the backbone of polymeric prodrugs for biologically active compounds [ 215 , 216 ]. Curcumin has potent antioxidant and ROS scavenging pharmacological effects because of the capacity of providing hydrogen atoms [ 217 ].…”

Redox Responsive Copolyoxalate Smart Polymers for Inflammation and Other Aging-Associated Diseases

“…Protein expression of caspase-3, Bcl-2, and Bax confirms the anti-apoptotic potential for the PVAX particle formulation. The integration of diagnosis and therapeutic nature of PVAX, using ultrasound imaging of musculoskeletal injuries was tested and proved to be an added advantage to age-related skeletal muscle dysfunction [ 46 ].…”