NAD+激酶
烟酰胺腺嘌呤二核苷酸
急性肾损伤
肾脏疾病
肾
线粒体
烟酰胺
药理学
癌症研究
化学
生物化学
医学
内科学
酶
作者
Ying Kong,Chen Xu,Feng Liu,Jiageng Tang,Yijing Zhang,Xiangxiang Zhang,Luyao Zhang,Tong Zhang,Yaqi Wang,Miaoda Su,Q Zhang,Hanxiang Chen,Di Zhou,Yi Fan,Hong Liu,Yi Fu
标识
DOI:10.1002/adma.202310731
摘要
Abstract As a central metabolic molecule, nicotinamide adenine dinucleotide (NAD + ) can potentially treat acute kidney injury (AKI) and chronic kidney disease (CKD); however, its bioavailability is poor due to short half‐life, instability, the deficiency of targeting, and difficulties in transmembrane transport. Here a physiologically adaptive gallic acid‐NAD + nanoparticle is designed, which has ultrasmall size and pH‐responsiveness, passes through the glomerular filtration membrane to reach injured renal tubules, and efficiently delivers NAD + into the kidneys. With an effective accumulation in the kidneys, it restores renal function, immune microenvironment homeostasis, and mitochondrial homeostasis of AKI mice via the NAD + ‐Sirtuin‐1 axis, and exerts strong antifibrotic effects on the AKI‐to‐CKD transition by inhibiting TGF‐β signaling. It also exhibits excellent stability, biodegradable, and biocompatible properties, ensuring its long‐term safety, practicality, and clinical translational feasibility. The present study shows a potential modality of mitochondrial repair and immunomodulation through nanoagents for the efficient and safe treatment of AKI and CKD.
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