Nanomaterials with intrinsic
enzyme-like activities (nanozymes) have emerged as promising agents for
cancer theranostics strategies. However, size-controllable synthesis of nanozymes and their targeting modifications are still challenging. Here, we report a monodispersed
ferritin-based
cobalt nanozyme (HccFn(Co3O4)) that specifically targets and visualizes clinical
hepatocellular carcinoma (HCC) tissues. The
cobalt nanozyme is biomimetically synthesized within the
protein shell of the HCC-targeted
ferritin (HccFn) nanocage, which is enabled by the display of HCC cell-specific
peptide SP94 on the surface of
ferritin through a genetic engineering approach. The intrinsic
peroxidase-like activity of HccFn(Co3O4) nanozymes catalyzes the substrates to make color reaction to visualize HCC
tumor tissues. We examined 424 clinical HCC specimens and verified that HccFn(Co3O4) nanozymes distinguish HCC tissues from normal liver tissues with a sensitivity of 63.5% and specificity of 79.1%, which is comparable with that of the clinically used HCC-specific marker α
fetoprotein. Moreover, the pathological analysis indicates that the HccFn(Co3O4) nanozyme staining result is a potential predictor of prognosis in HCC patients. Staining intensity is positively correlated to
tumor differentiation degree ( P = 0.0246) and
tumor invasion ( P < 0.0001) and negatively correlated with overall survival ( P = 0.0084) of HCC patients. Together, our study demonstrates that
ferritin is an excellent platform for size-controllable synthesis and targeting modifications of nanozymes, and the HccFn(Co3O4) nanozyme is a promising
reagent for prognostic diagnosis of HCC.