Ultra-small Platinum-based coordination nanoparticles for radiotherapy
Résumé
Radiation therapy is an effective and localised method of cancer treatment and its efficacy is considerably improved by using radiosensitizing agents. Nanoparticles containing high atomic number (Z) elements have emerged as an appealing class of sensitizers/enhancers. This work reports the first example of radiosensitizers based on ultrasmall platinum (Pt)polycyanometallate nanoparticles. Importantly, both novel nanosensitizers (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 the influence of 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 up to 60 % at larger doses. Furthermore, irradiation studies conducted on a model DNA probe evidence that in the presence of these novel Pt-based radiosensitizers, the amount of lethal Double Stranded Breaks (DSB) is significantly enhanced. The radiotherapeutic efficiency of these versatile coordination nanoparticles obtained using a cheap, fast and green process opens interesting possibilities in the field of nanomedicine.
Domaines
Chimie
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