Hybrid Nanoparticle Pyramids for Intracellular Dual MicroRNAs Biosensing and Bioimaging

This study strategically fabricates multifunctional nanopyramids to allow the ultrasensitive quantification of dual microRNAs (miR‐203^b and miR‐21) in living cells and their responsive bioimaging in vivo. The nanopyramids, composed of Au‐Cu₉S₅ nanoparticles (NPs), upconversion NPs (UCNPs), and Ag₂S NPs, emit two luminescent signals simultaneously with excitation at 808 nm, arising from the UCNPs at 541 nm in the visible region and from the Ag₂S NPs at 1227 nm in the second window of near‐infrared (NIR‐II) region. The upconversion luminescence has a linear relationship with miR‐203^b from 0.13 to 54.54 fmol per 10 µg_RNA and a limit of detection (LOD) of 0.09 fmol per 10 µg_RNA, whereas the Ag₂S NP luminescence has a linear relationship with miR‐21 from 0.37 to 43.56 fmol per 10 µg_RNA, with a LOD of 0.23 fmol per 10 µg_RNA. Significantly, this study demonstrates that the nanopyramids can be successfully used for miRs‐responsive bioimaging in a tumor‐bearing animal model. Furthermore, taking advantage of the photothermal capabilities of pyramids, the tumors can also be eliminated completely. These nanopyramids not only overcome the obstacles in the simultaneous detection of multiple miRs at the cellular level but also provide a cancer theranostic platform in vivo.