Melittin-loaded gold nanocages camouflaged by anti-MUC18 functionalized lipid bilayers for chemo-photothermal ablation of melanoma cells

Melittin (MEL), a potent apoptotic substance, holds promise for cancer treatment. However, due to its undesirable side, its direct use in humans is limited. On the other hand, gold nanocages (AuNCs) have gained attention as potential nanocarriers for cancer therapy due to their high loading capacity and photothermal effect. In this study, a targeted MEL-based delivery system in melanoma was developed by post-inserting anti-MUC18 single-chain antibodies modified polyethylene glycol (PEG)-lipid onto AuNCs, resulting in Immuno-liposomal layer modified AuNCs (AuNC@scFv-lip) with a hydrodynamic size of approximately 96 nm. The negatively charged surface of AuNCs allowed for a high loading efficiency of 93 % for MEL. MEL-loaded AuNCs@scFv-lip (MEL-AuNCs@scFv-lip) demonstrated dual acidic pH and near-infrared (NIR) irradiation-triggered release. Cellular internalization of AuNC@scFv-lip were investigated in A375 melanoma cells using flow cytometry, showing an approximately 18-fold higher cellular uptake compared to non-targeted liposomal layer modified AuNCs (AuNC@lip). Additionally, AuNC@scFv-lip was internalized via clathrin-dependent endocytosis, while AuNC@lip primarily utilized the caveolae-dependent pathway. MEL-AuNC@scFv-lip exhibited increased toxicity toward A375 cells compared to MEL-AuNC@lip. Moreover, the IC50 of MEL-AuNC@scFv-lip decreased in the presence of laser irradiation, combining MEL's cytotoxic effect with photothermal ablation of A375 cells. Overall, this multifunctional targeted nanocarrier possesses key structural characteristics, making it a promising candidate for remote-controlled combination therapy of melanoma.