Simple synthesis of amino acid-functionalized hydrophilic upconversion nanoparticles capped with both carboxyl and amino groups for bimodal imaging

The development of multimodal imaging probes carrying more than one modifiable site is very important in medical diagnosis. Herein, we demonstrate that amino acids, including acidic, neutral and basic amino acids, can be used as stabilizers and functional agents for the simple, one-step hydrothermal synthesis of hydrophilic upconversion nanoparticles (UCNPs) with a pure hexagonal phase and strong upconversion luminescence (UCL). The surface of the as-prepared UCNPs was capped with both carboxyl and amino groups, which not only provided the NPs with good dispersity in water, but also made further conjugation with two different biomolecules (e.g. targeted molecules and functional agents) possible. By co-doping different lanthanide ions, amino acid-functionalized UCNPs with different-colored UCL and different functions were obtained. For example, aspartate (Asp)-functionalized NaLuF₄ co-doped with Tm³⁺ and Gd³⁺ not only emitted strong UCL in the range of the biological transparent window, but also has great potential as a T₁-weighted magnetic resonance (MR) imaging contrast agent. The as-prepared Asp-NaLuF₄:Gd/Yb/Tm UCNPs were successfully used in the UCL/MR bimodal in vivo imaging of nude mice.