Immune-Evasive Biomimetic Gold-Carbon Nanoplatform for Dual-Modal Theranostics of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains refractory to systemic therapy due to poor tumor selectivity, rapid drug clearance, and acquired resistance to sorafenib (SF). Here, we report a membrane-engineered biomimetic gold-carbon theranostic nanoplatform (ARG-SF@M) that integrates immune evasion, homologous targeting, dual-modal imaging, and synergistic chemo-photothermal therapy (chemo-PTT) within a single nanosystem. The platform is constructed by co-assembling gold nanorods (AuNRs) and a fluorescent carbon nanomaterial (GTTN) for efficient SF loading, followed by cloaking with HCC cell membranes to confer prolonged circulation and tumor-homotypic recognition. AuNRs enable efficient near-infrared photothermal conversion and thermal imaging (TI), while GTTN provides stable fluorescence imaging (FI) for real-time biodistribution monitoring. The membrane camouflage markedly enhances tumor accumulation and reduces off-target distribution, thereby improving SF delivery efficiency. In vivo studies demonstrate that ARG-SF@M achieves a tumor inhibition rate of 81.92%, significantly higher than that of free SF (42.43%) and non-biomimetic ARG-SF (66.05%). Under NIR irradiation, tumor suppression further increases to 90.77%, substantially outperforming AuNRs + L (55.35%), confirming strong chemo-PTT synergy. Mechanistically, photothermal activation induces intratumoral hyperthermia, mitochondrial dysfunction, excessive reactive oxygen species generation, HSP70 upregulation, and activation of the mitochondrial apoptotic pathway. Collectively, this work presents a rational biomimetic membrane-engineering strategy for imaging-guided precision HCC theranostics.