KYF4:Yb,Er nanoparticles were fabricated and functionalized with streptavidin for the recognition of toll-like receptors (TLRs) on human neutrophil through biotinylated lipopolysaccharide (biotin-LPS). X-Ray diffraction, Infrared spectroscopy, Transmission Electron Microscopy and Agarose Gel Electrophoresis were used to characterize the as-prepared and functionalized nanoparticles. Confocal Scanning Laser Microscopy was applied to study the TLR specific recognition using KYF4:Yb,Er and the uptake of the nanoparticles functionalized with BSA/Dextran-streptavidin in the presence of biotin-LPS by human neutrophils under normal (37 ºC) and cell stressing conditions (4 ºC). Confocal microscopy studies showed that the uptake of the functionalized KYF4:Yb,Er nanoparticles occurs faster and with a higher rate at 37 ºC compared to the uptake at 4 ºC, indicating that the uptake mechanism is an energy dependent process. Research reported in this work provides relevant guidance for the development of lanthanide doped KYF4:Yb,Er nanoparticles as specific intracellular probes, allowing control of the nanoparticle-cell interactions by tuning the surface properties. Furthermore, our results would pave the way to the use of lanthanide-doped materials for imaging cellular processes such as uptake of nanoparticles and recognition of receptors involved in immune responses.