Metronidazole-functionalized iron oxide nanoparticles for molecular targeting of hypoxic tissue
Being crucial in several pathologic conditions, tumors, and tissue engineering, MRI tracing of the hypoxia within cells and tissues would be improved by the use of nanosystems allowing for direct targeting of low oxygenation and further treatment-oriented development. In the present study, we functionalized dendron-coated iron oxide nanoparticles (dendronized IONPs) with a bioreductive compound, a metronidazole-based ligand, to specifically recognize the hypoxic tissues. Spherical IONPs with an average size of 10 nm were obtained and then decorated with the new metronidazole-conjugated dendron. The resulting nanoparticles (metro-NPs) displayed negligible effects on cell viability, proliferation, and metabolism in both monolayer and 3D cell culture models, and a good colloidal stability into bio-mimicking media, as shown by DLS. Overtime quantitative monitoring of the IONP cell content revealed an enhanced intracellular retention of metro-NPs under anoxic conditions, confirmed by in vitro MRI of cell pellets where a stronger negative contrast generation was observed into hypoxic primary stem cells and tumor cells after labeling with metro-NPs. Overall, these results suggest desirable properties in terms of interactions with the biological environment and the active targeting of the hypoxic tissue, and indicate that metro-NPs have considerable potential for the development of new nano-platforms especially in the field of anoxia-related diseases and tissue engineered models.