Enhanced tumor immunohistochemical detection using a protein A-fused Pyrococcus furiosus ferritin carrier with...

Immunohistochemistry (IHC) is a cornerstone technique in tumor pathology. However, the detection of low-abundance antigens often requires high antibody input, increasing cost and limiting analytical efficiency. Here, we developed a novel ferritin-based nanocarrier system by genetically fusing Protein A to Pyrococcus furiosus ferritin (PA-PfFn), generating a multivalent scaffold for Fc-directed recruitment of HRP-conjugated secondary antibodies. The PA-PfFn-HRP polymer effectively amplifies detection signals through avid binding and enzymatic cascade reactions, enabling robust visualization of weakly expressed tumor markers. In a mouse glioma (U87) model, this strategy achieved higher detection sensitivity than conventional IHC and preserved robust staining performance even when primary antibody concentrations were reduced by up to 128-fold. By markedly lowering antibody consumption while maintaining staining intensity and specificity, this modular and tunable platform offers a practical, cost-effective approach for sensitive tumor biomarker detection and potential quantitative pathological analysis in both clinical and translational research settings.