Polyglycerol-amine Covered Nanosheets Target Cell-free DNA to Attenuate Acute Kidney Injury

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Abstract Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials has been regarded as a promising remedy for cfDNA-associated diseases. Nevertheless, the nanomaterials-based cfDNA scavenging tactic has not yet been reported in AKI treatment. Herein, polyglycerol-amine (PGA) covered MoS2 nanosheet with medium size (M-PGA-M) was erected to bind negatively charged cfDNA for AKI treatment. M-PGA-M exhibited excellent cfDNA scavenging efficacy and low cytotoxicity, which effectively reduced serum cfDNA levels, dominantly accumulated in kidney to inhibit neutrophil extracellular trap formation and inflammation, thereby alleviating LPS-induced AKI in mice. The renoprotective effects of M-PGA-M were superior to corresponding polymer PGA attributed to its unique two-dimensional nanostructure. Further, M-PGA-M showed to decrease serum cfDNA from AKI patients. Collectively, M-PGA-M could serve as a potent cfDNA scavenger, suggesting its potential application in treating AKI and other cfDNA-associated diseases. Teaser Scavenging cell-free DNA (cfDNA) with polyglycerol-amine (PGA)-covered MoS2 nanosheets may represent a novel treatment for AKI.

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