An intra articular injectable Mitocelle recovers dysfunctional mitochondria in cellular organelle disorders

• Published in: Bioactive materials 2025-01, Vol.43, p.305-318
• Main Authors: Lim, Min Ju, Oh, Hyeryeon, Jeon, Jimin, Cho, Chanmi, Lee, Jin Sil, Hwang, Yiseul, Kim, Seok Jung, Mo, Jung-Soon, Son, Panmo, Kang, Ho Chul, Choi, Won Il, Yang, Siyoung
• Format: Article
• Language: English
• Subjects: Acids; Alzheimer's disease; Arthritis; Biocompatibility; Biomedical materials; Cartilage; Cartilage diseases; Cellular manufacture; Cellular organelle disease; Chondrocytes; Degenerative diseases; Disease; Dysfunctional mitochondria; FDA approval; Federal regulation; Inflammation; Inhibition of NOX4-p22phox axis; Micelles; Mitocelle; Mitochondria; NOX4 protein; Osteoarthritis; Oxidative stress; Pathology; Pigments; Polyvinylpyrrolidone; Potassium; Povidone; Spectrum analysis
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.09.021

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. [Display omitted] •In this study, we show that Mitocelle, a povidone-templated Prussian blue nanozyme composed of FDA-approved materials, tracts NOX4-induced dysfunctional mitochondria for blocking Nox4-p22phox interaction.