In recent years, nano-
hydroxyapatite (
nHAp) based dual-/multi-modal bioimaging systems have received significant attention due to their excellent bioactivity and biocompatibility. Specifically, co-doping two or more
ions (such as Eu3+, Te3+, Gd3+ and Mn2+) into the lattice of
nHAp can directly endow
nHAp with multimodal imaging properties. However, the main strategy for the construction of co-doped
nHAp nanocrystals depends on high temperature and techniques of post-modification, which could lead to inevitable
nHAp crystal polymerization and increased particle size. Thus, the complexity of the preparation could further limit the clinical applications. Herein, based on the specific binding between
hyaluronan and CD44
protein, a biomimetic synthesis method using
hyaluronan as a template was explored for the construction of Eu/Ba co-doped and F-substituted
nHAp (HA@
nFAp:Eu/Ba) with recognition capability. The as-prepared HA@
nFAp:Eu/Ba nanocrystals possessed uniform and spindle-like morphology with good monodispersity. Compared with co-doped
nFAp that was synthesized under
hyaluronan-free and high-temperature hydrothermal conditions, this one-step synthesized HA@
nFAp:Eu/Ba presented improved doping efficiency and colloidal stability, realizing high sensitivity in both CT and fluorescence imaging. Besides, cytotoxicity studies indicated that the developed HA@
nFAp:Eu/Ba nanocrystals exhibited good compatibility in both cells and mice. Meanwhile, the HA@
nFAp:Eu/Ba nanocrystals also demonstrated
tumor targeted stability in both
cancer cells and living mice according to the favourable results from CT and fluorescence imaging. Therefore, this biomimetic synthesis strategy allowed multi-functionalization of
nHAp in one pot under mild conditions.