Semiconductor Nanocrystals and Copper Clusters for Radiotherapy: The Importance of the Coating and Composition for the Radio Incorporation of Cu64, Their Photo-and Colloidal- Stability

Cation exchange (CE) reactions on nanocrystals consists of the replacement of cations in the nanocrystalline structure with different metal ions while maintaining in place the anion framework. This technique has been extensively used for the synthesis of nanocrystals at different compositions. Here, we exploit CE reactions to radiolabel cadmium-free semiconductor NCs of ZnS, ZnSe and chalcopyrite (CuFeS<i>2</i>) NCs with Cu-64 radioisotope. [1] To make it possible a one-step CE protocol that is straightforward and highly efficient while maintaining good NC colloidal stability, the type of ligand coating to be chosen as water soluble stabilizer agents and the amount of Copper-64 to be exchanged were the key factors. This enabled to obtaining <i>64</i>Cu:CuFeS<i>2</i> in very high yields which did not require any further work out for the purification thus speeding up the radiolabeled NCs preparation. This unique approach of CE reaction enables to tune the specific activity in a wide range (from 2 to 100 TBq/g ) with an unprecedentedly record value of specific activity up to 100 TBq/g. In addition, among the NCs explored, CuFeS<i>2 </i> NCs [2] even after partial-CE reaction with Copper-64 were promising heat mediators for photo-thermal therapy (PPT). The synergic toxicity of photo-ablation and <i>64</i>Cu mediated radiotherapy ionization is here used to eliminate the glioblastoma and epidermoid carcinoma tumor cells. Further, as demonstrated with preliminary and unpublished results, the dual therapy is evaluated on xenograft mice models bearing epidermoid carcinoma tumor, resulting in elimination of solid tumor mass in mice. A modified version of this protocol was also established to obtain copper-64 radio-clusters of sub nanometer size and having also radio and photoluminescent properties. The optical stability of the copper clusters was tuned by controlling the size, coating and composition of the clusters and it will be also discussed.<br/><br/><b>References</b><br/><br/>[1] Avellini, T. et al, Adv. Funct. Mat. 2020, 30, 2002362<br/>[2] Ghosh, S. et al, Chem. Mater. 2016, 28, 13, 4848.