Cell membranes-encapsulated gadolinium-doped carbon dots for the efficient photothermal and immunotherapeutic synergistic treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a predominant subtype of liver cancer, is witnessing a rising global incidence and urgently demands the development of innovative nanoplatforms that integrate precise therapeutic and immune regulatory functions. To address the limitations of conventional monotherapies, which often suffer from inadequate tumor targeting, insufficient efficacy, and limited immune activation, this study employs a "biomimetic targeting-synergy therapy" approach. We have engineered a composite system consisting of gadolinium-doped carbon dots (Gd-CDs) enveloped with hepatocellular carcinoma cell membranes (HCM), thereby imparting homologous targeting capabilities and immune activation properties. This Gd-CDs@HCM system facilitates photothermal immunotherapy, guided by bimodal fluorescence (FL) and magnetic resonance (MR) imaging. Upon laser irradiation, Gd-CDs@HCM can induce immunogenic cell death (ICD) in tumor cells. The tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) released during ICD collaboratively enhance systemic anti-tumor immunity in conjunction with HCM, achieving a primary tumor ablation rate of 84.9% and inhibiting tumor progression. Consequently, this research offers an innovative strategy for real-time monitoring and precise synergistic treatment of HCC by utilizing FL/MR bimodal imaging and integrating bionic targeting, localized thermal ablation, and immune activation functions.