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A new type of highly selective aptamer-labeled fluorescent silica nanoparticles [Apt-tris(2,2′-bipyridyl)ruthenium(II)@SiO NPs] were prepared through the reverse microemulsion method by using prolonged fluorescence lifetime ruthenium complexes of tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)) as the source of the fluorescence for cellular prion protein imaging. Investigations showed that the newly prepared Ru(bpy)@SiO NPs possessed superior advantages of strong fluorescence, low toxicity, and easy surface modification for bioconjugation. Cell imaging experiments indicated that Apt-Ru(bpy)@SiO NPs had great tendency to human bone marrow neuroblastoma cells (SK-N-SH cells), since they can express large amount of prion protein on the surface of the cell, while in HeLa cells this phenomenon disappeared for the reason that HeLa cells cannot express prion proteins. [ABSTRACT FROM AUTHOR]