Core-Shell Structured Nanozyme with PDA-Mediated Enhanced Antioxidant Efficiency to Treat Early Intervertebral Disc Degeneration.

Early intervention during intervertebral disc degeneration (IDD) plays a vital role in inhibiting its deterioration and activating the regenerative process. Aiming at the high oxidative stress (OS) in the IDD microenvironment, a core-shell structured nanozyme composed of Co-doped NiO nanoparticle (CNO) as the core encapsulated with a polydopamine (PDA) shell, named PDA@CNO, was constructed, hoping to regulate the pathological environment. The results indicated that the coexistence of abundant Ni 3+ /Ni 2+ and Co 3+ /Co 2+ redox couples in CNO provided rich catalytic sites; meanwhile, the quinone and catechol groups in the PDA shell could enable the proton-coupled electron transfer, thus endowing the PDA@CNO nanozyme with multiple antioxidative enzyme-like activities to scavenge •O 2 - , H 2 O 2 , and •OH efficiently. Under OS conditions in vitro , PDA@CNO could effectively reduce the intracellular ROS in nucleus pulposus (NP) into friendly H 2 O and O 2 , to protect NP cells from stagnant proliferation, abnormal metabolism (senescence, mitochondria dysfunction, and impaired redox homeostasis), and inflammation, thereby reconstructing the extracellular matrix (ECM) homeostasis. The in vivo local injection experiments further proved the desirable therapeutic effects of the PDA@CNO nanozyme in a rat IDD model, suggesting great potential in prohibiting IDD from deterioration.