Lanthanide‐Doped LiLuF₄ Upconversion Nanoprobes for the Detection of Disease Biomarkers

Abstract

Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great promise in bioapplications. Exploring new host materials to realize efficient upconversion luminescence (UCL) output is a goal of general concern. Herein, we develop a unique strategy for the synthesis of novel LiLuF4 :Ln(3+) core/shell UCNPs with typically high absolute upconversion quantum yields of 5.0 % and 7.6 % for Er(3+) and Tm(3+) , respectively. Based on our customized UCL biodetection system, we demonstrate for the first time the application of LiLuF4 :Ln(3+) core/shell UCNPs as sensitive UCL bioprobes for the detection of an important disease marker β subunit of human chorionic gonadotropin (β-hCG) with a detection limit of 3.8 ng mL(-1) , which is comparable to the β-hCG level in the serum of normal humans. Furthermore, we use these UCNPs in proof-of-concept computed tomography imaging and UCL imaging of cancer cells, thus revealing the great potential of LiLuF4 :Ln(3+) UCNPs as efficient nano-bioprobes in disease diagnosis.

Inorganic lanthanide nanoprobes for background-free luminescent bioassays

“…With known isoelectric points, the ζ potentials of the NPs and the conjugating biomolecules can be readily tuned in opposite charges by adjusting the pH value of the reaction buffers, which allows for direct bioconjugation of the NPs via electrostatic attraction [100]. For example, by utilizing the positively charged Ln 3+ ions exposed on ligand-free LiLuF 4 :Yb, Er UCNPs, we have succeeded in the avidin functionalization of the UCNPs through electrostatic interaction [62]. Likewise, Lu and coworkers [101] developed an exceptionally simple strategy for the direct synthesis of DNA-func- -Benzotriazole-N,N,N',N'-tetramethyluronium-hexafluoro-phosphate (HBTU) and N,N-diisopropylethy (DIEA) as cross-linking reagents [65,102].…”

“…SLBL method, we further designed a unique strategy for the synthesis of multi-shell LiLuF 4 : Ln 3+ @LiLuF 4 upconversion (UC) NPs via thermal decomposition (Figs 2f-i) [62]. It was observed that the overall UCL intensity was remarkably enhanced upon successive shell passivation.…”

“…The selection criterion for the hosts of UCNPs is identical to that of their DSL counterparts. So far, the most efficient and widely used UCNPs is Yb/Er or Yb/Tm co-doped β-NaYF 4 , though some novel UC host materials such as β-NaLuF 4 and tetragonal-phase LiLuF 4 have been newly reported to have a higher UCL efficiency [62,[140][141][142][143].…”

“…For instance, utilizing the avidin-functionalized LiLuF 4 : Yb,Er@LiLuF 4 core-shell UCNPs as the nanoprobes, we realized the detection of β-hCG in the UCL microplate assay (Fig. 12a) [62]. It was observed that the UCL intensity of the nanoprobes gradually increased with the increased amount of β-hCG antigen and exhibited a linear dependence with the concentration of β-hCG at 0-310 ng mL −1 (Figs 12b and c).…”

Synthesis and Applications of Lanthanide-Doped Nanocrystals

“…In terms of the mechanism of luminescence, luminescence of Ln3+ ions can be divided into down-conversion and up-conversion emission processes. The down-conversion process is the conversion of higher-energy photons into lower-energy photons [2], which often requires two main components, an inorganic matrix (known as the host) and activated Ln3+ doping ions (activators). Hitherto, many types of inorganic compounds, such as oxides, fluorides, phosphates, and vanadates, have been widely used as host materials.…”