Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models.

ABSTRACT

The time interval between the diagnosis of tumor in a patient and the initiation of treatment plays a key role in determining the survival rates. Consequently, theranostics, which is a combination of diagnosis and treatment, can be expected to improve survival rates. Early detection and immediate treatment initiation are particularly important in the management of melanoma, where survival rates decrease considerably after metastasis. The present work reports for the first time the application of fluorescein isothiocyanate (FITC)-tagged epidermal growth factor receptor (EGFR)-functionalized ceria nanoparticles, which exhibit intrinsic reactive oxygen species (ROS)-mediated anticancer effects, for the EGFR-targeted diagnosis and treatment of melanoma. The theranostic activity was demonstrated using two-dimensional (2D) and three-dimensional (3D) models of parental and metastatic melanoma. Confocal imaging studies confirm the diagnostic activity of the system. The therapeutic efficiency was evaluated using cell viability studies and ROS measurements. The ROS elevation levels are compared across the 2D and 3D models. Significant enhancement in the generation of cellular ROS and absence in mitochondrial ROS are observed in the 2D models. In contrast, significant elevations in both ROS types are observed for the 3D models, which are significantly higher for the metastatic spheroids than the parental spheroids, thus indicating the suitability of this nanoformulation for the treatment of metastatic melanoma.