Glucose-functionalized gold nanoparticles for effective photothermal therapy in lung cancer

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnoses that severely limit therapeutic interventions. In this context, nanoparticle-mediated photothermal therapy (PTT) has emerged as a promising and minimally toxic modality for solid tumors. We synthesized gold nanoparticles (AuNPs) with three distinct morphologies-spheres, rods, and stars-and functionalized them with polyethylene glycol (AuNPs-PEG) or polyethylene glycol conjugated with 2-deoxy-D-glucose (AuNPs-Gluc). In vitro analyses using human (A549, H1299) and murine (LLC) lung carcinoma cell lines demonstrated that PEGylation significantly attenuated AuNP-associated cytotoxicity, while glucose functionalization further enhanced biocompatibility. Inductively coupled plasma mass spectrometry quantification confirmed superior cellular uptake of AuNPs-Gluc compared to AuNPs-PEG (p < 0.05). Subsequent irradiation with a 980 nm diode laser (1 W) induced robust thermal damage and apoptotic cell death selectively in cancer cells treated with AuNPs-Gluc, sparing non-tumoral cells. Among the morphologies tested, star-shaped AuNPs exhibited the highest photothermal efficiency. In vivo experiments further substantiated the therapeutic potential, as combined administration of AuNPs-Gluc and laser irradiation significantly suppressed tumor growth (p < 0.01). Collectively, these findings highlight the utility of glucose-functionalized AuNPs as effective vectors for targeted PTT in lung cancer, supporting their translational relevance for future clinical applications in advanced-stage disease.