Abstract
Sepsis is a life-threatening organ dysfunction responsible for nearly 270,000 deaths annually in the United States alone. Nicotinamide adenine dinucleotide (NAD+), an immunomodulator, can potentially treat sepsis; however, clinical application of NAD+ is hindered by its inability to be directly taken up by cells. To address this challenge, a family of nanoparticles (NPs) loaded with either NAD+ or the reduced form of NAD+ (NADH), hereafter NAD(H)-loaded NPs, were engineered to enable direct cellular transport and replenishment of NAD(H). The NAD(H)-loaded NPs improved cellular energy supply, suppressed inflammation and prevented inflammation-induced cell pyroptosis and apoptosis. Therefore, the NPs can help maintain immune homoeostasis and vascular function, two key factors in the pathogenesis of sepsis. The NAD(H)-loaded NPs demonstrated excellent therapeutic efficacies in treating endotoxemia and multidrug-resistant pathogen-induced bacteremia. In addition, the NAD(H)-loaded NPs prevented caecal ligation and puncture-induced multiorgan injury and improved outcomes of secondary Pseudomonas aeruginosa infections following caecal ligation and puncture, thus potentially leading to a highly innovative and translational approach to treat sepsis efficiently and safely.
【초록키워드】 Apoptosis, Inflammation, Pathogenesis, Infection, Sepsis, outcome, immune, immunomodulator, cells, pyroptosis, death, organ dysfunction, cellular, Bacteremia, Pseudomonas aeruginosa, Transport, NAD+, therapeutic efficacy, help, life-threatening, treat, key factor, multiorgan injury, Vascular function, NADH, multidrug-resistant, approach, Cell, responsible, the United State, addition, reduced, demonstrated, maintain, suppressed, prevented, translational, homoeostasis, 【제목키워드】 therapy, Sepsis, immune, vascular homeostasis, modulating,