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

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 and in a diabetic nephropathy mouse model, M-CDs administration significantly attenuated fibrotic responses and improved kidney function, 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 its kinase activity and downstream fibrotic responses. This finding definitively expands the functional scope of carbon dots from general anti-oxidant materials to precise, structure-based kinase inhibitors. Supported by rigorous biosafety profiles, this work establishes M-CDs as the bio-sourced carbon nanomaterial capable of direct kinase inhibition, offering a safe, effective, and mechanism-driven strategy against kidney fibrosis and potentially other kinase-mediated pathologies.