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.

脓毒症是一种危及生命的器官功能障碍，仅在美国每年就有近 27 万人死亡。烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 是一种免疫调节剂，有可能治疗败血症；^{然而，NAD +}的临床应用因其不能被细胞直接摄取而受到阻碍。为了应对这一挑战，我们设计了一系列负载 NAD ⁺或还原形式的 NAD ⁺ (NADH) 的纳米颗粒 (NP)（以下简称负载 NAD(H) 的 NP），以实现 NAD(H) 的直接细胞运输和补充。 ）。负载 NAD(H) 的 NP 改善了细胞能量供应，抑制炎症并防止炎症诱导的细胞焦亡和凋亡。因此，纳米颗粒可以帮助维持免疫稳态和血管功能，这是脓毒症发病机制的两个关键因素。负载NAD(H)的纳米粒子在治疗内毒素血症和多重耐药病原体引起的菌血症方面表现出优异的治疗效果。此外，负载NAD(H)的纳米粒子可以防止盲肠结扎和穿刺引起的多器官损伤，并改善盲肠结扎和穿刺后继发性铜绿假单胞菌感染的结果，从而可能导致一种高度创新和转化的方法来有效和安全地治疗脓毒症。