Assessment of Cytotoxicity and Protein Corona Formation of Β-Nalnf₄ Nanoparticles in Red Blood Cells

Lanthanide-doped nanoparticles (NPs) have unique photophisical properties that make them promising candidates for diverse technological applications. These materials combine the optical characteristics of lanthanide ions with the stability of the host matrix and the possibility of surface functionalization, enabling the development of multifunctional systems that can be explored in areas ranging from catalysis to nanomedicine. In particular, their use in nanomedicine is highly attractive given the need for advanced tools to understand complex pathophysiological processes, enabling more accurate diagnoses and therapeutic innovations. Although many studies explore these applications, systematic investigations into the impact of these NPs on human cells are still scarce. In this context, this work proposes an integrated approach to the synthesis and functionalization of core@shell NPs based on lanthanide fluorides (NaLnF4), as well as to evaluate their cytotoxicity and the influence of protein corona formation on their photophysical properties, targeting applications in biological systems. Core@shell NPs were designed to emit in the visible and near-infrared regions under excitation at 808 nm, a wavelength compatible with biological demands. Surface modification included the removal of oleic acid, resulting in ligand-free nanoparticles (LF), and functionalization with alendronate (AL). The cytotoxicity of NPs was evaluated by monitoring cell integrity and protein corona formation while photophysical characterizations were performed before and after interaction with blood plasma or hemolysate. Photophysical characterizations showed that protein corona formation did not affect the emission or luminescence lifetimes of LF and AL samples, upon interaction with blood plasma or hemolysate. In addition, hemolysis assays showed percentages below 5% for all samples, indicating non-harmful interactions between NPs@corona and red blood cells. Overall, these results demonstrate the low cytotoxicity of lanthanide-doped NPs, reinforcing their potential for application in biological systems. Furthermore, the preservation of their optical properties after protein corona formation highlights their suitability for optical sensing in nanomedicine applications.