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

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to latestage 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 AuNPassociated 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 (1W) 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.