Facile preparation of radium-doped, functionalized nanoparticles as carriers for targeted alpha therapy

Abstract

Despite its attractive properties, internal targeted alpha particle therapy using ^223/224Ra is currently limited to palliative bone-seeking applications. To make both radioisotopes accessible for the treatment of other cancer diseases, functionalized nanoparticles (NPs) based on BaSO₄ are proposed as carriers to stably bind radium to a targeting molecule. Although significant advances in the tailoring of BaSO₄-based NPs have been achieved, their preparation is strongly dependent on the use of surfactants and additives. Herein, the direct facile one-pot preparation of radium-doped, alendronate-functionalized BaSO₄ NPs from [²²⁴Ra]Ra(NO₃)₂, (NH₄)₂SO₄, BaCl₂ and alendronate in an aqueous medium has been reported. Remarkably, the size of the formed BaSO₄ NPs is independent of the anion used, but is controlled by the addition of organic solvents. Upon the addition of alendronate, amine functionalities were introduced on the NP surface. To evidence this modification, a fluorescent dye-containing alendronate was used. Additionally, a similar fluorescent NBD active ester was applied to prove the reactivity of the outer alendronate amine groups for a later connection of targeting molecules to follow the radiotherapeutic approach. The variations in the functionalities were examined by IR, and the morphology of the resulting BaSO₄ NPs was investigated in detail. DLS and TEM measurements showed that the average diameter of the nanoparticles was approx. 140 nm.