H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles

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􏰁􏰂􏰃 􏰅􏰆􏰇 􏰈􏰉􏰊􏰋􏰌􏰂􏰍 nanomaterials Article Diagnosis and Simultaneous Treatment of Musculoskeletal Injury Using H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles in a Rat Model of Contusion Injury Gi-Wook Kim 1,2,* , Nan-Hee Song 3 , Mi-Ran Park 3, Tae-Eon Kim 3, Da-Sol Kim 1,2 , Young-Bin Oh 4 and Dong-Won Lee 3,5,* Citation: Kim,G.-W.;Song,N.-H.; Park, M.-R.; Kim, T.-E.; Kim, D.-S.; Oh, Y.-B.; Lee, D.-W. Diagnosis and Simultaneous Treatment of Musculoskeletal Injury Using H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles in a Rat Model of Contusion Injury. Nanomaterials2021,11,2571. https:// doi.org/10.3390/nano11102571 Academic Editor: Eleonore Fröhlich Received: 30 August 2021 Accepted: 21 September 2021 Published: 30 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 2 3 4 5 Abstract: 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. Keywords: musculoskeletal injury; vanillin; polymer nanoparticles; ultrasound imaging; inflammation 1. Introduction Closed muscle contusion or trauma injury is a relatively common in the musculoskele- tal disorders. Acute tissue injuries occur when sudden and heavy forces are directly applied to the muscles. Chronic tissue injuries are caused by overuse, repetitive stress, sports ac- tivates, or incorrect mechanical movement [1–3]. The incidence varies from 10% to 55%, accounting for about 40% of musculoskeletal traumas in the young populations [1,3,4]. The clinical symptoms of contusion injuries are swelling, redness, local pain and tenderness during palpation. In severe cases, muscle weakness and decreased range of motion may occur [4]. The pathological progression following muscle contusion can be divided into three distinguished stages. First, the tissue destruction and inflammatory response occur 1 to 3 days after injury, and a large number of inflammatory cells infiltrate into the injury Department of Physical Medicine and Rehabilitation, Jeonbuk National University Medical School, Jeonju 54097, Korea; murunoon@naver.com Research Institute of Clinical Medicine of Jeonbuk National University—Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54097, Korea Department of Bionanotechnology and Bioconvergence Engineering, Jeonbuk National University, Jeonju 54896, Korea; nanhee9710@gmail.com (N.-H.S.); anne0189@naver.com (M.-R.P.); rotqhf94@jbnu.ac.kr (T.-E.K.) Department of Physical Medicine and Rehabilitation, Umji Clinic, Daejeon 33522, Korea; youngbiin@hanmail.net Department of Polymer Nano Science and Technology, Jeonbuk National University, Jeonju 54896, Korea * Correspondence: k26@jbnu.ac.kr (G.-W.K.); dlee@hjbnu.ac.kr (D.-W.L.) Nanomaterials 2021, 11, 2571. https://doi.org/10.3390/nano11102571 https://www.mdpi.com/journal/nanomaterials

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