Discovery of FGFBP1 as a novel target of isorhamnetin against LUSC and preliminary study of sea buckthorn-derived carbon dots

Abstract Lung squamous cell carcinoma (LUSC) remains a challenging malignancy with limited targeted therapies. Isorhamnetin (ISO), a natural flavonoid derived from sea buckthorn, exhibits promising antitumor activity. However, its molecular targets and underlying mechanisms in LUSC remain unclear. Concurrently, carbon dots (CDs) synthesized from herbal sources have emerged as promising nanoplatforms for cancer theranostics. This study aimed to elucidate the antitumor mechanism of ISO in LUSC and explore the potential of sea buckthorn-derived CDs as a functional nanomedicine. LUSC cells were treated with different concentrations (0, 50, 100 μM) of ISO. The effects on cell proliferation, migration, and invasion were assessed via CCK-8 assays, colony formation assays, scratch assays, and Transwell assays. Differentially expressed genes were screened through transcriptome sequencing, with key targets validated by Western blot analysis. Construct FGFBP1 overexpression cell lines for reversal experiments and detect downstream FGF2c/ERK signalling pathway-related protein expression. Additionally, sea buckthorn carbon dots (SB-CDs) were synthesised via hydrothermal synthesis using sea buckthorn as the carbon source. Characterisation was performed using X-ray photoelectron spectroscopy, ultraviolet–visible absorption spectroscopy, and fluorescence spectroscopy. Preliminary evaluation assessed their inhibitory effect on the malignant phenotype of LUSC cells. ISO significantly suppressed the proliferation, migration, and invasion of LUSC cells in a dose-dependent manner. Transcriptomics and protein analysis revealed that ISO downregulated fibroblast growth factor binding protein 1 (FGFBP1) and inhibited the downstream FGF2/ERK signaling pathway. Overexpression of FGFBP1 partially reversed the antitumor effects of ISO. Meanwhile, SB-CDs were successfully prepared with excellent fluorescence properties and effectively inhibited the malignant behaviors of LUSC cells in a concentration-dependent manner. ISO exerts its anti-tumour effects in LUSC by downregulating FGFBP1 and inhibiting the FGF2/ERK signalling pathway. Furthermore, sea buckthorn-derived carbon dots exhibit inherent antitumor properties, demonstrating a successful transformation from medicinal plant to functional nanomaterial. This study not only provides new insights into the mechanism of ISO but also offers a green and sustainable strategy for developing plant-based nano-theranostic agents against LUSC.