Target-Zippable Anisotropic Near-Infrared AuNRs for Highly Reliable and Bright SERS Imaging of miRNA <i>In Vivo</i>

Near-infrared surface-enhanced Raman scattering (NIR-SERS) probes are promising for <i>in vivo</i> molecular imaging, but they face challenges in balancing plasmonic activity and signal reproducibility. We designed target-zippable anisotropic NIR gold nanorod (ani-NIR-AuNR) SERS probes, whose end and side regions are decorated with catalytic hairpin assembly (CHA) DNA hairpins and Raman reporters, respectively. These ani-NIR-AuNR monomers maintain a near-zero background until triggered by targets to form uniform side-by-side dimers with an average gap of 0.88 nm, synergistically amplifying electromagnetic enhancement and chemical enhancement. The CHA allows one target to zip numerous dimers, boosting hotspot density. These effects endow the SERS probes with good reproducibility (RSD = 8.56%), superior sensitivity (LOD = 0.15 fM), and a broad linear range (1 fM to 1 nM) for let-7d detection. Compared to fluorescence probes, they offer higher brightness, better spatial resolution, and longer signal persistence in <i>in vivo</i> miRNA imaging, demonstrating substantial potential in bioapplications.