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Catalytic Nanodots-Driven Pyroptosis Suppression in Nucleus Pulposus for Antioxidant Intervention of Intervertebral
Kaiqiang Sun1,2, Chen Yan1, Xinyue Dai3
1Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, Shanghai, 200003, P. R. China.
Abstract:
Low back pain resulting from intervertebral disc degeneration (IVDD) is a prevalent global concern; however, its underlying mechanism remains elusive. Single-cell sequencing analyses revealed the critical involvement of pyroptosis in IVDD. Considering the involvement of reactive oxygen species (ROS) as the primary instigator of pyroptosis and the lack of an efficient intervention approach, this study developed carbonized Mn-containing nanodots (MCDs) as ROS-scavenging catalytic biomaterials to suppress pyroptosis of nucleus pulposus (NP) cells to efficiently alleviate IVDD. Catalytic MCDs have superior efficacy in scavenging intracellular ROS and rescuing homeostasis in the NP microenvironment compared with N-acetylcysteine, a classical antioxidant. The data validates that pyroptosis plays a vital role in mediating the protective effects of catalytic MCDs against oxidative stress. Systematic in vivo assessments substantiate the effectiveness of MCDs in rescuing a puncture-induced IVDD rat model, further demonstrating their ability to suppress pyroptosis. This study highlights the potential of antioxidant catalytic nanomedicine as a pyroptosis inhibitor and mechanistically unveils an efficient strategy for the treatment of IVDD.
Insights
This study introduces carbonized Mn-containing nanodots (MCDs) to combat intervertebral disc degeneration (IVDD) by scavenging reactive oxygen species (ROS) and inhibiting pyroptosis, offering a novel treatment strategy.
Area of Science:
- Biomaterials Science
- Cell Biology
- Orthopedics
Background:
- Intervertebral disc degeneration (IVDD) causes widespread low back pain, with mechanisms not fully understood.
- Pyroptosis, a form of inflammatory cell death, is implicated in IVDD pathogenesis.
- Reactive oxygen species (ROS) are key triggers of pyroptosis, necessitating effective interventions.
Purpose of the Study:
- To develop novel carbonized Mn-containing nanodots (MCDs) for ROS scavenging.
- To investigate MCDs' efficacy in suppressing pyroptosis in nucleus pulposus (NP) cells.
- To evaluate MCDs as a therapeutic strategy for IVDD.
Main Methods:
- Single-cell sequencing to identify pyroptosis involvement in IVDD.
- Development and characterization of MCDs as ROS-scavenging agents.
- In vitro assessment of MCDs' effect on NP cells and ROS levels.
- In vivo evaluation of MCDs in a rat model of IVDD.
Main Results:
- MCDs demonstrated superior ROS-scavenging capacity compared to N-acetylcysteine.
- MCDs effectively suppressed pyroptosis in NP cells and restored NP microenvironment homeostasis.
- MCD treatment significantly alleviated IVDD in a rat model by inhibiting pyroptosis.
Conclusions:
- Pyroptosis is a critical mediator in IVDD and a viable therapeutic target.
- Antioxidant catalytic nanomedicine, specifically MCDs, shows promise for inhibiting pyroptosis.
- MCDs represent an efficient nanomedicine strategy for treating intervertebral disc degeneration.
