Mitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases.The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expect...Mitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases.The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expected to disrupt mitochondrial function.However,the field lacks a competitive inhibitor of the NOX4-p22phox interaction.Here,we created a povidone micelle-based Prussian blue nanozyme that we named“Mitocelle”to target the NOX4-p22phox axis,and characterized its impact on the major degenerative cellular organelle disease,osteoarthritis(OA).Mitocelle is composed of FDA-approved and biocompatible materials,has a regular spherical shape,and is approximately 88 nm in diameter.Mitocelle competitively inhibits the NOX4-p22phox interaction,and its uptake by chondrocytes can protect against mitochondrial malfunction.Upon intra-articular injection to an OA mouse model,Mitocelle shows long-term stability,effective uptake into the cartilage matrix,and the ability to attenuate joint degradation.Collectively,our findings suggest that Mitocelle,which functions as a competitive inhibitor of NOX4-p22phox,may be suitable for translational research as a therapeutic for OA and cellular organelle diseases related to dysfunctional mitochondria.展开更多
基金supported by the National Research Foundation,funded by the Ministry of Science&ICT(2021M3C1C3097647,NRF-2022R1A2C2004343,RS-2023-00223552,and RS-2024-00335111)the Korea Healthcare Technology R&D project of the Korea Health Industry Development Institute(HI16C0001 and HR22C1734)+1 种基金a Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korea government(the Ministry of Science and ICT,the Ministry of Health&Welfare,23C0113L1)the Korea Institute of Ceramic Engineering and Technology(KICET,2410002182).
文摘Mitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases.The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expected to disrupt mitochondrial function.However,the field lacks a competitive inhibitor of the NOX4-p22phox interaction.Here,we created a povidone micelle-based Prussian blue nanozyme that we named“Mitocelle”to target the NOX4-p22phox axis,and characterized its impact on the major degenerative cellular organelle disease,osteoarthritis(OA).Mitocelle is composed of FDA-approved and biocompatible materials,has a regular spherical shape,and is approximately 88 nm in diameter.Mitocelle competitively inhibits the NOX4-p22phox interaction,and its uptake by chondrocytes can protect against mitochondrial malfunction.Upon intra-articular injection to an OA mouse model,Mitocelle shows long-term stability,effective uptake into the cartilage matrix,and the ability to attenuate joint degradation.Collectively,our findings suggest that Mitocelle,which functions as a competitive inhibitor of NOX4-p22phox,may be suitable for translational research as a therapeutic for OA and cellular organelle diseases related to dysfunctional mitochondria.
