Editors' ChoiceOsteoarthritis

Keeping nanoparticles within the joint

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Science Translational Medicine  16 Oct 2019:
Vol. 11, Issue 514, eaaz3716
DOI: 10.1126/scitranslmed.aaz3716


Manganese dioxide nanoparticles target chondrocytes, protecting cartilage tissue from inflammation-induced oxidative damage.

Osteoarthritis (OA) is caused by degeneration of joint cartilage and underlying bone,; it is a leading cause of disability across the Western world. By 2030 it is estimated that about 25% of adults in the United States will suffer from this condition. Remarkably, neither a cure nor disease-modifying treatments exist. One common feature that appears to mark OA is oxidative stress, the buildup of reactive oxygen species (ROS) like hydrogen peroxide (H2O2), which can lead to inflammation and degradation of cartilage. Several compounds have been investigated to target oxidative stress in OA; however, results have been unconvincing. Two challenges exists for OA treatment development. First, although compounds can be injected directly into a joint, joints are inheritantly leaky and compounds are rapidly cleared from joints within days. Second, targeting cells which generate cartilage (chondrocytes) is difficult because cartilage is avascular and chondrocytes are sparsely populated throughout the cartilage matrix.

Kumar et al. sought to engineer a therapeutic that would overcome the issue of bioavailability in the joint to effectively target oxidative stress in chondrocytes. The authors engineered ROS-scavinging nanoparticles that could penetrate and remain in cartilage tissue. The nanoparticles were made from manganese dioxide (MnO2), which catalyzes the breakdown of H2O2, one of the main ROS produced by chondrocytes. The nanoparticles were engineered to be positively charged to be attracted to negatively charged proteoglycans and were 20 nm in size to fit within the spacing of the extracellular matrix of cartilage. The nanoparticles were biocompatible, penetrated the cartilage matrix, and were internalized by chondrocytes; particles were retained in the joint for 7 days when injected intra-articularly in rats. In a bovine explant model in which cartilage explants were challenged with interleukin-1β to induce oxidative stress and inflammation-mediated cartilage degradation, treatment with nanoparticles protected chondrocytes through antioxidant control.

Although conducted in bovine explants and rodents, this study represents a successful application of MnO2 nanoparticles for cartilage protection. Further studies will need to confirm findings using in vivo models of osteoarthritis before translation to humans, but this study represents an exciting advance that overcomes some of the challenges of developing treatments for osteoarthritis.

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