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.
Shahbazkhani et al. (Fri,) studied this question.