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Upconversion nanoparticles (UCNPs) are widely used in the field of biomedicine, such as biosensing, cell labeling and medical multimodal imaging because of their unique optical properties. In this paper, we demonstrated the synthesis of polyethylenimine-modified NaLuF4:Yb,Er (RE = Lu 0.78, Yb 0.18, Er 0.02) UCNPs in three different solvents, such as water, ethylene glycol and diethylene glycol. The as-prepared UCNPs were characterized and the experimental results showed that the UCNPs synthesized in ethylene glycol had excellent properties. The obtained UCNPs in ethylene glycol had the smallest particle size and uniform size distribution, and the pure cubic phase of crystallization and Dynamic light scattering and particle dispersion index (DLS/Pdi) were the smallest. What's more, the upconversion fluorescence intensity was 7 and 52 times greater than that of UCNPs synthesized in diethylene glycol and water, respectively. In addition, the factors of reaction solvent that had an impact on the particle size, morphology, crystalline phase, DLS and upconversion fluorescence intensity of the synthesized UCNPs were discussed. Moreover, in order to obtain the targeted nanoprobe, we used an EDC/NHS covalent coupling method to modify folic acid to the NaLuF4:Yb,Er/PEI UCNP surface. The NaLuF4:Yb, Er/PEI–FA upconversion fluorescent nanoprobes had low cytotoxicity and were suitable for the application in HeLa cells targeted fluorescent imaging.
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