Isoginkgetin-loaded reactive oxygen species scavenging nanoparticles ameliorate intervertebral disc degeneration via enhancing autophagy in nucleus pulposus cells

Abstract

Excessive reactive oxygen species (ROS) in nucleus pulposus cells (NPCs) promote extracellular matrix (ECM) degradation and cellular inflammatory responses by activating a variety of cellular pathways, ultimately inducing cell apoptosis and leading to the development of low back pain. Here, we designed and fabricated an isoginkgetin-loaded ROS-responsive delivery system (IGK@SeNP) based on diselenide block copolymers. Successfully encapsulated IGK was released intelligently and rapidly in a microenvironment with high ROS levels in degenerative disc. Controlled-release IGK not only efficiently scavenged ROS from the intervertebral disc together with diselenide block copolymers but also effectively enhanced autophagy in NPCs to inhibit ECM degradation and cell apoptosis, and showed significant therapeutic effects in the rat intervertebral disc degeneration (IDD) model. Overall, the synergistic effects of IGK@SeNP in ROS scavenging and autophagy enhancement endowed it with an attractive therapeutic strategy for IDD treatment.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems

“…It has shown promise as a potential therapeutic agent for IVDD. In a study conducted by Yu et al, a selenium–selenium (Se–Se) bond-containing nanodelivery system was developed to carry IGK (IGK@SeNP). This delivery system exhibited ROS-responsiveness and demonstrated excellent biocompatibility.…”

“…Demonstration of inflammation suppression and restoration of ECM homeostasis in IVDD rat models. Reproduced with permission from Wang et al 38 49 a selenium−selenium (Se−Se) bond-containing nanodelivery system was developed to carry IGK (IGK@SeNP). This delivery system exhibited ROS-responsiveness and demonstrated excellent biocompatibility.…”

Stimuli-Responsive Delivery Systems for Intervertebral Disc Degeneration

“…Yu et al constructed a ROS-responsive IGK-loaded nanodelivery system (IGK@SeNP) and achieved its smart release under the stimulation of excessive ROS. 89 The IGK@SeNP system contained Se-Se bonds and exhibited excellent biocompatibility. Se-Se bonds and IGK play a joint role in clearing ROS.…”

“…Further testing in a rat needle puncture IVDD model showed that this intelligent system has superior efficacy for treating IVDD in vivo. 89 …”

“…Further testing in a rat needle puncture IVDD model showed that this intelligent system has superior efficacy for treating IVDD in vivo. 89 Bai et al designed an in situ-formed rapamycin-loaded ROS-scavenging scaffold and offered a new strategy for promoting IVDD tissue regeneration. 90 In an oxidative environment, the scaffold consumed ROS and gradually released rapamycin.…”