Theranostic CuS Nanoparticles Targeting Folate Receptors for PET/CT Image-Guided Photothermal Ablation Therap

617 Objectives 64Cu-labeled copper sulfide nanoparticles (CuS NPs) have been proposed as a single-compartment theranostic nanoplatform for positron emission tomography (PET) imaging and photothermal ablation (PTA) therapy (J Am Chem Soc 132:15351, 2010). However, there has no report to date on active targeting of CuS NPs to tumor cells. The purpose of this study was to synthesize a novel class of folate receptor-targeted CuS (FA-CuS) NPs, and evaluate the PET/CT image-guided therapeutic effects of these NPs for PTA therapy in KB tumor xenografts. Methods FA-CuS NPs and non-targeted PEG-CuS NPs were synthesized and characterized with regard to size and stability. Tumor uptake and biodistribution of NPs were studied by microPET/CT imaging. For antitumor activity, nude mice bearing s.c. folate receptor-positive KB tumors were injected i.v. with saline, PEG-CuS NPs, or FA-CuS NPs, followed by treatment with NIR laser at 1.5 W/cm2 for 2 min. Twenty-four hours after laser treatment, tumors were removed for histological evaluation. Results The successful synthesis of FA-CuS NPs with hydrodynamic diameter of ~21 nm was confirmed by transmission electron microscopy, dynamic light scattering analysis, UV-Vis spectrum, and 1H nuclear magnetic resonance. The uptake of FA-CuS NPs in KB cancer cells overexpressing the folate receptors was significantly blocked by free FA, indicating that the cellular uptake of the NPs was mediated by a receptor-mediated endocytosis process. microPET/CT imaging and biodistribution studies revealed that FA-CuS NPs exhibited significantly higher tumor uptake in nude mice bearing KB cancer xenografts than non-targeted NPs following intravenous administration. Important, PTA therapy with targeted FA-CuS NPs mediated substantially greater tumor necrosis than with non-targeted PEG-CuS NPs. Conclusions FA-CuS NPs are promising NPs for PET imaging-guided PTA of cancer cells that overexpress folate receptors.