Native MicroRNA Targets Trigger Self‐Assembly of Nanozyme‐Patterned Hollowed Nanocuboids with Optimal Interparticle Gaps for Plasmonic‐Activated Cancer Detection

The modernized use of nucleic acid (NA) sequences to drive nanostructure self-assembly has given rise to a new class of designed nanomaterials with controllable plasmonic functionalities for broad surface-enhanced Raman scattering (SERS)-based bioanalysis applications. Herein, dual usage of microRNAs (miRNAs) as both valuable cancer biomarkers and direct self-assembly triggers is identified and capitalized upon for custom-designed plasmonic nanostructures. Through strict NA hybridization of miRNA targets, Au nanospheres selectively self-assemble onto hollowed Au/Ag alloy nanocuboids with ideal interparticle distances (≈2.3 nm) for optimal SERS signaling. The intrinsic material properties of the self-assembled nanostructures further elevate miRNA detection performance via nanozyme catalytic SERS signaling cascades. This enables fM-level miR-107 detection limit within a clinically-relevant range without any molecular target amplification. The miRNA-triggered nanostructure self-assembly approach is further applied in clinical patient samples, and showcases the potential of miR-107 as a non-invasive prostate cancer diagnostic biomarker. The use of miRNA targets to drive nanostructure self-assembly holds great promise as a practical tool for miRNA detection in disease applications.