Gadolinium-Doped Carbon Nanodots as Potential Anticancer Tools for Multimodal Image-Guided Photothermal Therapy and Tumor Monitoring
Nicolò Mauro, Roberta Cillari, Cesare Gagliardo, Mara Andrea Utzeri, Maurizio Marrale, Gennara Cavallaro
Abstract
High Resolution Image Download MS PowerPoint Slide 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, GdCl 3, and urea. The incorporation of Gd 3+ 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 Gd 3+ 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 T 1 -weighted magnetic resonance imaging (MRI) experiments. MRI acquisitions at different Gd 3+ 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.