Anti-glioma efficacy of Quercetin-Iron nanodots with peroxidase-mimicking activity and photothermal conversion capability

Glioma remains one of the most aggressive brain tumors, necessitating innovative therapeutic strategies. Quercetin (Que), a natural polyphenolic flavonoid, has shown potential in cancer treatment. It can form iron-based nanodots (Que-Fe) that exhibit peroxidase (POD)-mimicking activity. This study aimed to synthesize and characterize Que-Fe nanodots, evaluate their photothermal conversion capabilities, and assess their anti-tumor efficacy both in vitro and in vivo. Que-Fe was synthesized through the coordination of Que with iron ions, yielding nanodots approximately 10 nm in diameter, confirmed by transmission electron microscopy and dynamic light scattering (DLS). The nanodots demonstrated significant POD-like activity in the presence of hydrogen peroxide. Photothermal experiments revealed that Que-Fe effectively converted near-infrared light into heat, achieving temperatures above 62 °C, indicating its potential as a photothermal agent. In vitro studies showed that Que-Fe exhibited concentration-dependent cytotoxicity against C6 glioma cells, with enhanced effects when combined with NIR irradiation. Transcriptomic analysis revealed that Que-Fe treatment upregulated genes associated with ferroptosis and oxidative stress, suggesting a multifaceted mechanism of action. In vivo experiments using a BALB/c nude mouse model demonstrated that Que-Fe, particularly in combination with NIR, significantly inhibited tumor growth and induced apoptosis without notable toxicity. Overall, these findings suggest that Que-Fe is a promising candidate for glioma therapy, leveraging its photothermal properties and inducing ferroptosis to enhance anti-tumor efficacy.