Dual Single-Atom Engineered NADH Oxidase-Mimic Boosts In Situ NAD⁺ Biotransformation for Targeted Myocardial...

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Nanomedicine

Background:

• Myocardial ischemia/reperfusion (I/R) injury is a critical condition causing organ dysfunction.
• Nicotinamide adenine dinucleotide (NAD+) supplementation shows potential for I/R injury but faces delivery and efficacy challenges.

Purpose of the Study:

• To develop a dual single-atom nanozyme for in situ NAD+ biotransformation and myocardial I/R injury treatment.
• To overcome the limitations of current NAD+ supplementation strategies.

Main Methods:

• Designed a nanozyme with NADH oxidase-mimicking activity and M2 macrophage membrane coating.
• Evaluated the nanozyme's targeting, NAD+ biotransformation, ROS scavenging, and anti-inflammatory effects in I/R injury models.
• Investigated the nanozyme's mechanism involving the NAD+-SIRT1 axis and inflammatory pathways.

Main Results:

• The nanozyme selectively targeted ischemic myocardium and facilitated in situ NAD+ biotransformation by eliminating excess NADH.
• Nanozyme treatment restored mitochondrial bioenergetics, reduced inflammation, and inhibited apoptosis.
• Mechanistic studies confirmed activation of the NAD+-SIRT1 axis and suppression of TNF and NF-κB signaling.

Conclusions:

• The engineered NOX-like nanozyme represents a novel therapeutic strategy for myocardial I/R injury.
• The nanozyme effectively modulates mitochondrial function and oxidative stress by restoring NAD+/NADH homeostasis.
• This approach offers improved clinical applicability for treating I/R injury.