Polyphosphoric acid capping radioactive/upconverting NaLuF4:Yb,Tm,153Sm nanoparticles for blood pool imaging in vivo

Nanoparticles that circulate in the bloodstream for a prolonged period of time have important biomedicine applications. However, no example of lanthanide-based nanoparticles having a long-term circulation bloodstream has been reported to date. Herein, we report on difunctional radioactive and upconversion nanoparticles (UCNP) coated with polyphosphoric acid ligand, that is ethylenediamine tetramethylenephosphonic acid (EDTMP), for an application in single-photon emission computed tomography (SPECT) blood pool imaging. The structure, size and zeta-potential of the EDTMP-coated nanoparticles (EDTMP-UCNP) are verified using transmission electron microscopy and dynamic light scattering. Injection of radioisotope samarium-153-labeled EDTMP-UCNP (EDTMP-UCNP:(153)Sm) into mice reveal superior circulation time compared to control nanoparticles coated with citric acid (cit-UCNP:(153)Sm) and (153)Sm complex of EDTMP (EDTMP-(153)Sm). The mechanism for the extended circulation time may be attributed to the adhesion of EDTMP-UCNP on the membrane of red blood cells (RBCs). In vivo toxicity results show no toxicity of EDTMP-UCNP at the dose of 100 mg/kg, validating its safety as an agent for blood pool imaging. Our results provide a new strategy of nanoprobe for a long-term circulation bloodstream by introducing polyphosphoric acid as surface ligand.