Post-Synthesis Incorporation of 64Cu in CuS Nanocrystals to Radio label Photothermal Probes: A Feasible Approach for Clinics

We report a simple method for the incorporation of Cu(I) or Cu-64(I) radionuclides in covellite nanocrystals (CuS NCs). After the in situ reduction of Cu(II) or Cu-64(II) ions by ascorbic acid, their incorporation in PEG-coated CuS NCs takes place at room temperature. In all the reaction steps, the stability of the NCs under physiological conditions was ensured. The copper incorporation reaction could also take place on CuS NCs bearing biotin molecules at their surface, with no detrimental effects on the specific binding affinity of the NCs toward streptavidin after incorporation. At low loading of Cu ions, the strong near-infrared (NIR) absorption band of the starting CuS NCs was essentially preserved, which allowed for efficient plasmonic photothermal therapy. The combined presence in the NCs of Cu-64 ions, well suitable for positron emission tomography, and of free carriers responsible for the NIR absorption, should enable their theranostic use as radiotracers and as photothermal probes in tumor ablation treatments. Moreover, the simplicity of the preparation scheme, which involves the use of radioactive species only as a last step, makes the protocol easily transferable to the clinical practice.