Large-scale one-pot synthesis of water-soluble and biocompatible upconversion nanoparticles for dual-modal imaging

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attentions in the area of molecular imaging, targeted therapy and diagnosis. The UCNPs synthesized by conventional methods are usually hydrophobic and require additional surface modification to give them water solubility and biocompatibility. Herein, we designed a simple and convenient strategy for the direct synthesis of water-soluble and biocompatible lanthanum-doped UCNPs through a one-pot reaction without further purification and screening. The doping amount of lanthanide can be adjusted by simply changing the proportion of precursor in the reaction solution. The resulting water-soluble UCNPs possess excellent colloidal stability in physiological media. Under 980 nm excitation, NaGdF₄:Yb³⁺/Er³⁺ and NaGdF₄:Yb³⁺/Tm³⁺ nanoparticles exhibited a dominant green emission band (⁴S_3/2→⁴I_15/2) of Er³⁺ and a dominant blue emission band (¹G₄→³H₆) of Tm³⁺, respectively. Toxic response was not observed with concentration up to 50 mg/L. The hemolysis to rabbit red blood cells was less than 2% in the concentration up to 20 mg/L. The NaGdF₄:Yb³⁺/Er³⁺ nanoparticles exhibited a high r₁ relaxivity of 4.7 mM^-1s^-1, demonstrating that the water-soluble and biocompatible UCNPs can be efficient T₁ contrast agents. The in vivo results show that UCNPs exhibit excellent T₁-weighted imaging and fluorescence imaging abilities simultaneously, and can be used as a versatile promising theranostic nanoplatform.