Work

Mulberry-derived carbon dots attenuate kidney fibrosis through direct inhibition of PI3K

Year: 2025

Type: article

Abstract: Kidney fibrosis is a progressive pathological process underlying chronic kidney disease, yet effective anti-fibrotic therapeutics remain scarce. Here, we developed fluorescent carbon dots derived from mulberry (M-CDs) via a facile hydrothermal method as a novel nanotherapeutic agent against kidney fibrosis. The obtained M-CDs exhibited excellent water dispersibility, high quantum yield, and outstanding fluorescence stability across broad pH and ionic strength conditions. In vitro, M-CDs dose-dependently inhibited TGF-β-mediated epithelial-mesenchymal transition and the upregulation of fibrotic markers in human renal tubular cells. In a diabetic nephropathy mouse model, M-CDs oral administration significantly improved kidney function, reduced extracellular matrix deposition, and ameliorated histopathological damage, demonstrating efficacy comparable to metformin. Mechanistic studies combining transcriptomics, cellular thermal shift assay, and molecular dynamics simulations revealed that M-CDs directly bind to the PI3K complex, inhibiting the PI3K/AKT signaling pathway and downstream fibrotic responses. Importantly, comprehensive in vitro and in vivo biosafety assessments confirmed the high biocompatibility of M-CDs. Our work not only introduces a bio-derived carbon dot with potent anti-fibrotic activity but also unveils its mechanism of action through direct kinase interaction, highlighting the great potential of M-CDs as a safe and effective nanotherapeutic for treating kidney fibrosis.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.102626