Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

Currently, there are no clinical drugs available to treat acute kidney injury (AKI). Given the high prevalence and high mortality rate of AKI, the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot. Although existing evidence fully demonstrates that reactive oxygen and nitrogen species (RONS) burst at the AKI site is a major contributor to AKI progression, the heterogeneity, complexity, and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects. Recently, nanodrugs with intrinsic kidney targeting through the control of size, shape, and surface properties have opened exciting prospects for the treatment of AKI. Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments. In this review, we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy. First, we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI: hypoxia, harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI.