Spatially Engineered Janus Hybrid Nanozyme toward SERS Liquid Biopsy at Nano/Microscales

Nanomaterials with intrinsic enzyme-mimicking properties (nanozymes) have been widely considered as artificial enzymes in biomedicine. However, manipulating inorganic nanozymes for multivariant targeted bioanalysis is still challenging because of the insufficient catalytic efficiency and biological blocking effect. Here, we rationally designed a spatially engineered hollow Janus hybrid nanozyme vector (h-JHNzyme) based on the bifacial modulation of Ag-Au nanocages. The silver face inside the h-JHNzyme served as an interior gate to promote the enzymatic activity of the Ag-Au nanozyme, whereas two-dimensional DNAzyme-motif nanobrushes deposited on the exterior surface of the h-JHNzyme endowed it with the targeting function and tremendously enhanced the peroxidase-mimicking activity. We demonstrated that the spatially separated modulation of the h-JHNzyme propelled it as a powerful "all-in-one" enzymatic vector with excellent biocompatibility, specific vectorization, remarkable enzymatic performance, and clinical practicability. Further, we programmed it into a stringent catalytic surface-enhanced Raman scattering (SERS) liquid biopsy platform to trace multidimensional tumor-related biomarkers, such as microRNAs and circulating tumor cells, with a limit of detection of fM and single cell level, respectively. The developed enzymatic platform showed great potential in facilitating reliable quantitative SERS liquid biopsy for on-demand clinical diagnosis.