β-Glucan nanotubes loaded with iron diselenide for enhanced photothermal and photodynamic therapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a significant global health challenge with limited treatment options, particularly for patients in advanced stages. Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising treatment modalities; however, their efficacy is often limited when used individually. Using the photothermal and photosensitive properties of iron diselenide (FeSe), this study evaluates β-glucan nanotubes loaded with BFP-FeSe nanocomposites for enhanced HCC treatment combining PTT and PDT. We evaluated cellular uptake and in vitro therapeutic effects, as well as in vivo antitumor efficacy and biosafety in a liver cancer mouse model of the loaded nanocomposites were evaluated. In vitro experiments demonstrated that BFP-FeSe2 was efficiently internalized by liver cancer cells. Its antitumor efficacy was significantly enhanced under near-infrared light irradiation (NIR), inducing immunogenic cell death. In vivo experiments further revealed that BFP-FeSe achieved a high tumor inhibition rate (92-98 %) while maintaining biosafety by activating immune responses and promoting T-cell infiltration into tumor tissues. These findings highlight BFP-FeSe nanocomposites as an original phototherapeutic agent for HCC treatment, offering high therapeutic efficacy with minimal systemic toxicity. STATEMENT OF SIGNIFICANCE: Liver cancer remains a major global health burden with limited treatment options, particularly in advanced stages. Photothermal and photodynamic therapies (PTT/PDT) offer promising alternatives, but their efficacy is often restricted when used alone. Our study introduces β-glucan nanotubes loaded with BFP-FeSe nanocomposites, leveraging the superior photothermal and photosensitive properties of FeSe₂ for synergistic PTT/PDT treatment. We demonstrate significant tumor inhibition (92-98 %) and immune activation with minimal toxicity in a liver cancer model. This work highlights a novel nanoplatform that enhances therapeutic outcomes while ensuring biosafety, offering new possibilities for HCC treatment. Our findings contribute to the growing field of nanomedicine and immunotherapy, with broad implications for cancer treatment strategies.