Work

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

Year: 2024

Type: article

Abstract: 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. An intra articular injectable Mitocelle tracks dysfunctional mitochondria, and alleviates cartilage damage by targeting the NOX4-p22phox axis. • 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.

Source: Bioactive Materials

DOI: 10.1016/j.bioactmat.2024.09.021