Ultra-small platinum-based coordination nanoparticles for radiotherapy

Abstract

Radiation therapy is an effective and localised method for cancer treatment and its efficacy is considerably improved by using radioenhancing agents. Nanoparticles containing high atomic number (Z) elements have emerged as an appealing class of enhancers. This work reports the first example of radioenhancers based on ultrasmall platinum (Pt)-polycyanometallate nanoparticles. Importantly, both novel nano-enhancers (Pt[Pt(CN)₄] and Pt[Fe(CN)₆]) are prepared in fairly large quantities using a water-based, surfactant-free, green route. The post-coating of the inorganic cores by different biocompatible polymers is straightforward and allows probing of the influence of the coating on the radiotherapeutic efficiency of the nanosystems. The structural/chemical integrity is maintained after high doses of γ-radiation and high colloidal stability is obtained in biological media. At 250 μM total metal concentration, these nanoparticles are non-toxic to cells, but when coupled with γ-radiation, they amplify apoptosis of HeLa cells by 20% at 4.5 Gray, which rises to 60% at larger doses. Furthermore, irradiation studies conducted on a model DNA probe evidence that the amount of lethal Double Strand Breaks (DSB) is significantly enhanced in the presence of these novel Pt-based radioenhancers. The radiotherapeutic efficiency of these versatile coordination nanoparticles obtained using a cheap, fast and green process opens interesting possibilities in the field of nanomedicine.