Multifunctional CuS Nanoparticles for Imaging Guided Photothermal Ablation Therapy

Statement of the problem: A process for rapid synthesis of radioactive [64Cu]CuS nanoparticles was successfully developed in our collaborator, Dr. Chun Li’s group. Further investigation shows that [64Cu]CuS nanoparticles can act as an efficient radiotracer for PET imaging, and can be used for photothermal ablation therapy using near-infrared laser irradiation (Zhou, Zhang et al. 2010). Based on these novel [64Cu]CuS NPs, we have designed and investigated two different types of NPs for targeting delivery and dual imaging agents. Methods: The NPs were charaterized with particle size, zeta potential, UV-vis spectroscopy, and photothermal effect in aqueous solution. The cytotoxicity was tested in HepG2, HEK293 and U87 cell lines. The tumor binding activity and the photothermal effect for the targeted CuS NPs was evaluated in U87 cells. PET/CT imaging, biodistribution and PTA therapy were performed in a U87 xenograft mouse tumor model. For the doped NPs, the elements quantification, MRI relaxivity and MRI imaging were also investigated. Results: The tumor uptakes at 24 h after i.v. injection for targeted [64Cu]CuS NPs and [64Cu]CuS-PEG NPs was about 10% and 5% ID/g, respectively. The PTA results revealed the 100 % necrotic area in tumor for the mice treated with targeted CuS NPs, compared with the 60% necrotic area for the ones treated with non-targeted CuS NPS. The MRI relaxivity was calculated based on the concentration of Mn ions. The r1 and r2 values were 5.9 (s mM)-1 and 110.7 (s mM)-1, respectively. The PET/CT imaging confirmed the accumulation of the radiolabeled [64Cu][Mn]CuS-PEG NPs in the tumor 24 h after i.v. injection. [Mn]CuS-PEG NPs exhibited 80% of necrotic area in tumor after PTA therapy.Pharmacological and Pharmaceutical Sciences, Department o