Paving a pathway for bright red-emitting Eu-loaded albumin nanoparticles fabrication

Lanthanide complexes with organic ligands exhibit unique photophysical properties, including long-lived emission lifetimes, large Stokes shifts, and sharp emission bands, making them highly attractive for bioanalytical and biomedical applications. Incorporating these complexes into nanoparticles can further enhance signal intensity and assay sensitivity in both in vitro and in vivo settings. Here, we report the first successful use of the desolvation method to synthesize bovine serum albumin (BSA) nanoparticles loaded with europium complexes. This simple approach involved the dropwise addition of an ethanolic solution of europium complex precursors into an aqueous BSA solution, followed by thermal cross-linking to generate disulfide bonds. We systematically optimized synthesis parameters—including pH, precursor concentration, and addition rate—to produce nanoparticles with high brightness and low polydispersity. Under optimized conditions, the resulting nanoparticles exhibited a uniform size of 150–160 nm (PDI<0.15) as determined by dynamic light scattering and electron microscopy. Each nanoparticle encapsulated approximately 350 europium complexes, achieving quantum yields of 0.77–1.18% with excitation/emission maxima at 360/615 nm. The synthesis yield was ~80%, and the nanoparticles demonstrated excellent size stability across physiological pH conditions and after three months of storage. However, luminescence intensity decreased over time and under certain buffer conditions. Cytotoxicity studies using Vero cells showed cell viability above 80% at nanoparticle concentrations up to 1 mg/mL. The key challenges to be addressed are the improvement of synthesis reproducibility and the stability of luminescent properties.