Gadolinium-Doped Carbon Nanodots as Potential Anticancer Tools for Multimodal Image-Guided Photothermal Therapy and Tumor Monitoring

Abstract

This study focuses on the synthesis and characterization of gadolinium-doped carbon nanodots (CDs-Gd) and their potential applications in multimodal imaging and precision cancer therapy. CDs-Gd were synthesized through a solvothermal decomposition method combining citric acid, GdCl3, and urea. The incorporation of Gd3+ ions within the carbonaceous structure resulted in stable CDs-Gd with a peculiar architecture that retained optical and paramagnetic properties. Combined characterization techniques confirmed the presence of pH-sensitive COOH functions on the CDs-Gd surface along with the unique lattice structure induced by Gd3+ doping. The optical properties of CDs-Gd exhibited a tunable emission spectrum displaying blue-green emission with pH-dependent behavior. Additionally, CDs-Gd exhibited contrast-enhancing properties in T1-weighted magnetic resonance imaging (MRI) experiments. MRI acquisitions at different Gd3+ concentrations and pH values demonstrated the potential of CDs-Gd as contrast agents for monitoring pH changes in an aqueous environment. We found that the relaxivity of CDs-Gd at pH 5.5 (tumor, 11.3 mM–1 s–1) is roughly 3-fold higher than that observed at pH 7.4 (physiological, 5.0 mM–1 s–1) and outperformed clinical standards such as γ-butyrol (3.3 mM–1 s–1). Monitoring pH changes in tumor microenvironment (TME) is crucial for evaluating the effectiveness of anticancer treatments and understanding tumor progression. Furthermore, CDs-Gd demonstrated concentration-dependent photothermal conversion ability in the near-infrared (NIR) region, allowing for efficient heat generation under laser irradiation. This indicates the potential application of CDs-Gd in image-guided photothermal therapy (IG-PTT) for cancer treatment. The in vitro studies on MCF-7 (breast cancer) and 16-HBE (healthy bronchial epithelium) cell lines demonstrated that CDs-Gd exhibited high biocompatibility (cell viability >80%). However, upon NIR activation, they showed potent anticancer effects by inhibiting tumor cell proliferation and inducing apoptosis selectively in cancer cells. In conclusion, the synthesized CDs-Gd nanoparticles possess unique optical, photothermal, and MRI contrast properties, making them promising candidates for multimodal imaging-guided precision cancer therapy applications.