Neodymium-embedded ultrasmall biomimetic calcium phosphate clusters for fluorapatite nanodot formation and NIR-II bioimaging

The limited concurrent NIR-II reservoir of fluorophores that simultaneously possess high brightness and excellent biocompatibility hampers the clinical translation of NIR-II. Herein, we host neodymium (Nd³⁺) into biomimetic calcium phosphate clusters (CPCs) as nuclei to crystallize into fluorapatite (FAP) nanodots, and report a novel type of lanthanide-based NIR-II nanoprobes. Results show that the doped Nd³⁺ forms more strongly coordinated and compact nanoclusters with phosphate in CPCs with an ultrasmall size of 2.61 ± 0.24 nm. Moreover, the up-conversion process of Nd in CPCs is nearly inhibited and exhibits intense and characteristics of down-conversion NIR-II photoluminescence. The lifetime of the excited states (Nd: ⁴F_3/2) in CPCs locate at the microsecond level and is temperature-independent from 80 K to 320 K. To raise the absolute photoluminescence quantum yield (PLQY) of Nd-CPCs, the clusters are further crystallized into Nd-FAP nanocrystals. The Nd-FAP nanocrystals are of nanodots shape and show aspect ratio of 1.53 with an average length of 7.70 ± 1.11 nm, and diameter of 5.02 ± 0.64 nm, and the PLQY is calculated to be 0.526 ± 0.053 %. Following PEGylation for enhanced hydrophilicity, the NIR-II nanoprobe enables real-time, non-invasive in vivo imaging of mouse organs and the popliteal lymph node. This new host system may be developed as a versatile platform to design and prepare other new NIR-II probes (praseodymium, holmium, and thulium-doped), MRI agents (gadolinium-doped) and even multiplexed/multimodal biomarkers, which may hold great potential in in vitro or in vivo bioimaging and biosensing applications.