Dual‐Mode Nanoprobes Based on Lanthanide Doped Fluoride Nanoparticles Functionalized by Aryl Diazonium Salts for Fluorescence and SERS Bioimaging

Abstract The design of dual‐mode fluorescence and Raman tags stimulates a growing interest in biomedical imaging and sensing applications as they offer the possibility to synergistically combine the versatility and velocity of fluorescence imaging with the specificity of Raman spectroscopy. Although lanthanide‐doped fluoride nanoparticles (NPs) are among the most studied fluorescent nanoprobes, their use for the development of bimodal fluorescent‐Raman probes has never been reported yet, to the best of the authors knowledge, probably due to the difficulty to functionalize them with Raman reporter groups. This gap is filled herein by proposing a fast and straightforward approach based on aryl diazonium salt chemistry to functionalize Eu³⁺ or Tb³⁺ doped CaF₂ and LaF₃ NPs by Raman scatters. The resulting surface‐enhanced Raman spectroscopy (SERS)‐encoded lanthanide‐doped fluoride NPs retain their fluorescence labeling capacity and display efficient SERS activity for cell bioimaging. The potential of this new generation of bimodal nanoprobes is assessed through cell viability assays and intracellular fluorescence and Raman imaging, opening up unprecedented opportunities for biomedical applications.