Polyacrylic acid complexes to mineralize ultrasmall europium-doped calcium phosphate nanodots for fluorescent bioimaging

Abstract

Nano calcium phosphate (nCaP), a bone mineral in mammals, shows a promising prospect in biomedicine. Herein, we report a biomimetic mineralization strategy, based on stoichiometric polyacrylic acid (PAA) complexation-precipitation process, to facilitate the development of nCaP as bioimaging agents. As a result, the monodisperse and sub-10 nm europium-doped calcium phosphate nanodots (PAA-Eu:CaP NDs) is controllably obtained with enhanced fluorescence properties, tumor passive targeting and bioimaging ability. Compared with europium-doped calcium phosphate nanoparticles (Eu:CaP NPs), the fluorescence emission, quantum yield and lifetime of PAA-Eu:CaP NDs are significantly improved up to 3.84, 4.48 and 5.59 times, respectively. Deriving from the synergy of surface effect and organic/inorganic hybrid crystal field effect, such CaP matrix brings to local asymmetry environment and distinguished anti-quenching for Eu3+ ion. The strongest radiance signal is improved to 117 % for in vivo imaging; moreover, the tumor accumulation is obviously increased to 5.15 times, and 7.09 times for tumor permeability. The accumulation is decreased 80.2 %, 79.4 % and 70.2 % in liver, spleen and lung suggesting lower clearance by mononuclear phagocyte system, while it’s increased up to 15.4 times in kidney indicating higher renal clearance. Eventually, it’s convinced that this study can provide help for promoting CaP application in nanomedicine.