Synthesis and characterization of biologically stable, doped LaF_3 nanoparticles co-conjugated to PEG and photosensitizers

There has been significant recent interest in combining radiation therapy and photodynamic therapy for cancer treatment. One proposed method involves conjugating photosensitizers (PS) to scintillating nanoparticles. However, the production of nanoscintillators that are stable in biological media is problematic since many of the commonly used compositions chelate phosphate. In this paper, the problem was solved by first synthesizing LaF3 nanoparticles, followed by surface modification with alendronate, which serves as a stable anchor for conjugation of molecules of interest. The nanoparticles had an average diameter of 4 nm, and were doped with either Ce^(3+), Tb^(3+), or both. In every case, a LaF3 shell was added. In subsequent steps, poly(ethylene) glycol (PEG) and photosensitizers (either chlorin e6 or rose bengal) were covalently linked to the alendronate ligand via an amide bond. This new formulation is stable in several solutions and buffers used commonly in the laboratory for cell culture. Moreover, cellular uptake and lack of toxicity up to a concentration of 50 μM were observed in B16 murine melanoma cells. Energy transfer between the doped nanoparticle core and the conjugated photosensitizers was demonstrated using UV excitation, and scintillation was demonstrated using x-rays