Abstract

The clinical translation of nanomedicine is frequently hampered by insufficient tumor accumulation and off-target toxicity. To overcome these limitations, we engineered a biomimetic nanoplatform, CGNS@CCM, for targeted photothermal-chemotherapy. The system integrates gold nanostars (GNS) as a photothermal core, a polydopamine (PDA) layer for drug loading, and a homologous cancer cell membrane (CCM) derived from HeLa cells as a camouflage. The resulting construct achieves a high photothermal conversion efficiency (39.5%) and enables near-infrared (NIR)-triggered doxorubicin (DOX) release in the acidic tumor microenvironment. The CCM cloak conferred effective immune evasion and homotypic targeting, which collectively enhanced cellular uptake and cytotoxicity in HeLa cells compared to non-camouflaged counterparts. In vivo studies using a HeLa xenograft model demonstrated superior tumor targeting and prolonged blood circulation of CGNS@CCM. A single administration followed by NIR irradiation potently suppressed tumor growth by over 80%, inducing extensive apoptosis and necrosis without observable systemic toxicity. This work underscores the promise of cell membrane-camouflaged nanotechnology as a safe and efficient strategy for precision cancer therapy.