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In the present paper, we use zinc oxide nanoparticles under the excitation of ultraviolet (UV) light for the generation of Reactive Oxygen Species (ROS), with the aim of further using these species for fighting cancer cells in vitro. Owing to the difficulties in obtaining highly dispersed nanoparticles (NPs) in biological media, we propose their coating with a double-lipidic layer and we evaluate their colloidal stability in comparison to the pristine zinc oxide NPs. Then, using Electron Paramagnetic Resonance (EPR) coupled with the spin-trapping technique, we demonstrate and characterize the ability of bare and lipid-coated ZnO NPs to generate ROS in water only when remotely actuated via UV light irradiation. Interestingly, our results reveal that the surface chemistry of the NPs greatly influences the type of photo-generated ROS. Finally, we show that lipid-coated ZnO NPs are effectively internalized inside human epithelial carcinoma cells (HeLa) via a lysosomal pathway and that they can generate ROS inside cancer cells, leading to enhanced cell death. The results are promising for the development of ZnO-based therapeutic systems.

Lipid-Coated Zinc Oxide Nanoparticles as Innovative ROS-Generators for Photodynamic Therapy in Cancer Cells