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

ABSTRACT 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.