Key result
Cardiac-targeted NAD+ nanoparticles reduce infarct size and improve cardiac function in preclinical ischemia-reperfusion models.
Why the study?
Effective therapies for myocardial ischemia-reperfusion injury after acute myocardial infarction remain limited. Although NAD+ plays a central role in mitochondrial function and redox homeostasis, its therapeutic application is hindered by poor membrane permeability and inefficient restoration of intracellular NAD+ pools.
Answers are grounded in this paper and cite their sources.
Preclinical NAD+ nanoparticles show promise; leaves open clinical translation for reperfusion injury.
Myocardial ischemia-reperfusion injury remains a major cause of cardiomyocyte loss and adverse remodeling following acute myocardial infarction, yet effective therapeutic options remain limited. Although nicotinamide adenine dinucleotide (NAD+) plays a central role in mitochondrial function and redox homeostasis, its therapeutic application is limited by poor membrane permeability and inefficient restoration of intracellular NAD+ pools. Here, we developed a cardiac-targeted lipid-polymer hybrid nanoparticle (LN-DPC) that enables efficient intracellular delivery of NAD+ to ischemic myocardium. The nanoparticale integrates boronate-guanidine-mediated NAD+ encapsulation with an ischemic myocardium-homing peptide (CSTSMLKAC), achieving stable loading, controlled release, and preferential accumulation in injured cardiac tissue. In vitro, LN-DPC enhanced cellular uptake and restored intracellular NAD+ levels, leading to improved mitochondrial function, reduced reactive oxygen species generation, and alleviation of calcium overload under OGD/R conditions. In vivo, the nanoparticles preferentially accumulated in the injured myocardium, attenuated early inflammation, significantly reduced infarct size, improved cardiac function, and markedly limited chronic fibrosis. Mechanistically, NAD+ delivery restored SIRT3 expression, improved mitochondrial homeostasis, and suppressed HMGB1-RAGE signaling to mitigate secondary myocardial injury; pharmacological SIRT3 inhibition attenuated the protective effects of LN-DPC both in vitro and in vivo, supporting a functional contribution of SIRT3 to LN-DPC-mediated cardioprotection. Collectively, this work establishes targeted NAD+ delivery as an effective strategy to restore metabolic homeostasis and protect against ischemia-reperfusion injury, and provides a nanomedicine platform for metabolic intervention in cardiovascular diseases.
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Xie et al. (2026) studied Myocardial ischemia-reperfusion injury. Cardiac-targeted lipid-polymer hybrid nanoparticle encapsulating NAD+ (LN-DPC) was evaluated on Infarct size, cardiac function, early inflammation, and chronic fibrosis. Cardiac-targeted NAD+ nanoparticles (LN-DPC) significantly reduced infarct size, improved cardiac function, and limited chronic fibrosis in preclinical myocardial ischemia-reperfusion models.
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