Biomimetic PNM@D@BP nanosheets protect kidneys from nephrocalcinosis via ROS scavenging and NETosis inhibition

Calcium oxalate (CaOx) nephrocalcinosis is a chronic kidney disease characterized by crystal deposition, oxidative stress, and neutrophil infiltration, leading to renal tubular epithelial cell injury. Currently, no targeted therapies are clinically available for this condition. Antioxidant nanomaterials that scavenge excessive reactive oxygen species (ROS) offer a promising therapeutic avenue. Additionally, inhibiting neutrophil extracellular traps (NETs), which contribute to inflammation, presents another critical target for mitigating kidney injury in this context.

Researchers developed a biomimetic nanoplatform, PNM@D@BP, by loading DNase I onto black phosphorus nanosheets (BPNSs) and coating them with a neutrophil membrane modified with a CD44-targeting peptide. This design aimed to enhance targeting specificity to inflamed renal sites. The platform's efficacy was evaluated in both in vivo and in vitro models of CaOx crystal-induced kidney injury. Key assessments included antioxidative activity, suppression of NET formation, and modulation of inflammatory responses, with insights gained from RNA sequencing and bioinformatic analyses.

PNM@D@BP nanosheets demonstrated potent antioxidative activity, effectively eliminating CaOx crystal-induced ROS. The engineered neutrophil membrane coating successfully conferred the nanocarrier with the ability to home to sites of renal injury and inflammation. In both in vivo and in vitro settings, PNM@D@BP was shown to suppress the formation of neutrophil extracellular traps (NETs). This dual action directly addresses key pathological drivers of nephrocalcinosis. Furthermore, RNA sequencing and bioinformatic analyses revealed that PNM@D@BP protects against CaOx crystal-induced kidney injury by modulating oxidative stress and neutrophil-driven inflammatory responses.