Rescuing Nucleus Pulposus Cells from ROS Toxic Microenvironment via Mitochondria‐Targeted Carbon Dot‐Supported Prussian Blue to Alleviate Intervertebral Disc Degeneration

Abstract

Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration of mitochondrial function and senescence in nucleus pulposus cells (NPCs). Significantly, the main ROS production site in non‐immune cells is mitochondria, suggesting mitochondria is a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which is known as mitochondrial‐tropic ligands, is utilized to modify carbon dot‐supported Prussian blue (CD‐PB) to scavenge superfluous intro‐cellular ROS and maintain NPCs at normal redox levels. CD‐PB‐TPP can effectively escape from lysosomal phagocytosis, permitting efficient mitochondrial targeting. After strikingly lessening the ROS in mitochondria via exerting antioxidant enzyme‐like activities, such as superoxide dismutase, catalase, etc CD‐PB‐TPP rescues damaged mitochondrial function and NPCs from senescence, catabolism, and inflammatory reaction in vitro. Imaging evaluation and tissue morphology assessment in vivo suggest that disc height index, mean grey values of nucleus pulposus tissue, and histological morphology were significantly improved in the IVDD model after CD‐PB‐TPP locally performed. In conclusion, this study demonstrates that ROS‐induced mitochondrial dysfunction and senescence of NPCs leads to IVDD and the CD‐PB‐TPP possesses enormous potential to rescue this pathological process through efficient removal of ROS via targeting mitochondria, supplying a neoteric strategy for IVDD treatment.This article is protected by copyright. All rights reserved

The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy

“…Rats had a surgery in IVDD group. There were other surgical procedures (Jia et al 2024 ; Wang et al 2006 ; Shi et al 2024 ; Zhang et al 2024 ). p21 and p53 protein expression were increased in degenerative discs of rats while they were reduced after NR treatment.…”

Target-Oriented Synthesis of Triphenylphosphine Functionalized Carbon Dots with Negative Charge for ROS Scavenging and Mitochondrial Targeting

“…Triphenylphosphine (TPP), which is lipophilic and positively charged, has been successfully applied for mitochondrial targeting driven by the potential difference with the mitochondrial membrane. − The fact that TPP and its derivatives are widely available also means that TPP can be assigned a wide range of functional groups. Thus, TPP was routinely combined with CDs to synthesize triphenylphosphine functionalized carbon dots (TPP-CDs) for target recognition and imaging of mitochondria .…”