A Pathological Microenvironment-Responsive Catalytic Carbon Nanodots Release Platform Intercepting the...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Intervertebral disc degeneration (IVDD) is driven by oxidative stress and inflammation.
• Reactive oxygen species (ROS) are key contributors to the degenerative cascade in IVDD.
• Current treatments lack targeted delivery and efficient ROS scavenging.

Purpose of the Study:

• To develop a microenvironment-responsive drug delivery platform for IVDD.
• To create a system for on-demand release of antioxidants to combat ROS.
• To investigate the therapeutic potential of this platform in IVDD.

Main Methods:

• Development of a dual cross-linked hydrogel (PPOD@CeCDs) responsive to acidic and oxidative conditions.
• Incorporation of cerium-doped carbon nanodots (CeCDs) as catalytic antioxidants.
• In vitro studies on nucleus pulposus (NP) cells and in vivo studies using a rat IVDD model.

Main Results:

• PPOD@CeCDs demonstrated injectability, controlled release, and biocompatibility.
• The platform protected NP cells from oxidative damage and suppressed inflammation via the PI3K-Akt-NF-κB pathway.
• In vivo, it reduced matrix degradation and promoted structural recovery in degenerative discs.

Conclusions:

• The microenvironment-responsive hydrogel effectively delivers antioxidants to intercept ROS-driven inflammation in IVDD.
• This strategy offers a promising therapeutic approach for IVDD by targeting the oxidative origin of inflammation.
• The integrated system provides a mechanistically defined and translationally relevant treatment for IVDD.