Baicalein-loaded silk fibroin peptide nanofibers protect against cisplatin-induced acute kidney injury: Fabrication, characterization and mechanism

Silk fibroin (SF) is a natural polymeric biomaterial widely used in the preparation of drug delivery systems. Herein, silk fibroin peptide (SFP) was self-assembled into nanofibers, encapsulated a poorly water-soluble drug baicalein (SFP/BA NFs), and then used to protect against cisplatin-induced acute kidney injury (AKI). Specifically, the SFP/BA NFs significantly enhanced the aqueous dispersity, storage stability, and in vitro antioxidant activity of BA. SFP/BA NFs increased the drug uptake and localization to mitochondria. In vitro results demonstrated that SFP/BA NFs can relieve the cisplatin-induced HK-2 cell damage, and inhibit the cisplatininduced accumulation of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) disruption. Mechanism studies demonstrated that SFP/BA NFs may exert nephmprotective effects by inhibiting both the cisplatin-induced DNA damage and the cGAS/STING pathway activation. In vivo results showed that cisplatin treatment resulted in decreased body weight, increased serum creatinine (SCr), and increased blood urea nitrogen (BUN) levels, while SFP/BA NFs reversed the above symptoms. Furthermore, SFP/BA NFs reversed the cisplatin-induced abnormal changes of antioxidant enzymes (e.g., SOD and GSH), and inhibited the cisplatininduced DNA damage as well as the activation of cGAS/TING. Above all, our results revealed the potential of SFP/BA NFs to protect against cisplatin-induced AKI.

Automated summary

In this study, silk fibroin peptide/baicalein nanofibers were used to protect against cisplatin-induced acute kidney injury. The nanofibers enhanced the water solubility and antioxidant activity of baicalein, and relieved cisplatin-induced cell damage and oxidative stress. Mechanism studies revealed that the nanofibers exerted their protective effects by inhibiting DNA damage and the activation of the cGAS/STING pathway.