Aptamer-PEG-modified Fe3O4@Mn as a novel T1- and T2- dual-model MRI contrast agent targeting hypoxia-induced cancer stem cells

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Abstract
Hypoxia-induced cancer stem cells have been known to be involved in tumour metastasis, resistance to chemo/radio therapy and tumour recurrence. Magnetic Resonance Imaging is a widely used imaging tool for cancers in clinics and research. To develop T1-positive and T2-negative dual mode MRI agents for more comprehensive and accurate diagnostic information under hypoxic conditions, a hypoxia-inducible factor-1α based aptamer and Mn(II)-modified nanoparticles D-Fe3O4@PMn were synthesized and characterized. In vitro and in vivo studies show that D-Fe3O4@PMn NPs are biocompatible and less cytotoxic and can produce significant contrast enhancement in T1- and T2-weighted MR imaging. Furthermore, the D-Fe3O4@PMn NPs enable targeted dual-contrast T1- and T2-weighted MR imaging of cancer cells expressing high levels of HIF-1α and cancer stem cell-related proteins under hypoxic condition. In conclusion, NPs with HIF-1α and Mn(II) are promising diagnostic agents for dual-mode T1 and T2 imaging by targeting cancer stem cells as they are non-toxic and biocompatible.

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