Theragnostic Gold Nanoparticle Contrast Agents for CT Imaging

Extensive efforts have been dedicated to the design, synthesis, and development of contrast agents with improved safety and multifunctionality for CT imaging applications. In this study, a theragnostic gold nanoparticle-based contrast agent was developed for integrated CT imaging and cancer therapy by conjugating the antifolate drug pemetrexed to PEGylated gold nanoparticles via click chemistry, using ethanolamine as a multifunctional linker. The resulting biocompatible and highly stable AuNPs (∼21 nm) exhibited promising X-ray attenuation, providing approximately 2-fold higher CT contrast compared with the commercial iodine-based agent Visipaque. Comprehensive physicochemical characterization was performed using FT-IR, DLS, 1H NMR, TGA, TEM, and UV–Vis spectroscopy. In vitro evaluations demonstrated enhanced anticancer activity of PMX-Et-AuNPs against the SH-SY5Y human neuroblastoma cell line, with a significantly lower IC50 value (0.185 μg/mL) compared with free pemetrexed and bare AuNPs, indicating a nanoparticle-mediated synergistic effect. In vivo microCT imaging revealed pronounced tumor accumulation and prolonged blood circulation following intravenous administration. Importantly, therapeutic efficacy studies in tumor-bearing mice demonstrated significant tumor growth inhibition and improved survival for PMX-Et-AuNP-treated groups compared with controls, without observable systemic toxicity, as confirmed by stable body weight and unaltered liver and renal function markers. Overall, these results highlight the potential of PMX-Et-AuNPs as a promising, safe theragnostic nanoplatform for simultaneous CT imaging and cancer treatment.