Synergistic self-calibration strategy based on nano-cornucopia MOFs for accurate HER-2 detection in precision breast cancer diagnosis.

With its high porosity and tunable properties, metal-organic frameworks (MOFs) serve as nano-cornucopias, unlocking limitless possibilities in biosensing applications. Herein, we designed an ultrasensitive biosensor leveraging MOFs as a multifunctional nano-platform to implement a synergistic self-calibration strategy for the ultra-accurate quantification of breast cancer-related human epidermal growth factor receptor-2 (HER-2). This approach integrates (1) ratiometric electrochemistry for built-in correction to minimize non-specific interference and (2) dual-modal electrochemical and colorimetric detection for enhanced accuracy through cross-validation. Functionalized NH-UiO-66 (Zr-MOF) was employed as a carrier to incorporate a dual-layer of anthraquinone-2-carboxylic acid (AQ), creating NH-UiO-66@AQ, a highly electroactive nanomaterial for signal amplification. The incorporation of gold nanoparticles (AuNPs) and ionically reduced graphene oxide (IL-rGO) further enhanced conductivity and electrochemical response. Additionally, MOF@FeTCPP nanozyme was synthesized by encapsulating iron (III) meso-tetra(4-carboxyphenyl) porphyrin chloride (FeTCPP) into HKUST-1 (Cu-MOF), demonstrating exceptional peroxidase-like activity. Coupling this nanozyme with streptavidin (SA) resulted in the formation of a dual-signal nanozyme probe (DSN-Probe) capable of generating both electrochemical and colorimetric signals. The biosensor exhibited a broad detection range (100 fg/mL to 150 ng/mL) with an ultra-low limit of detection (LOD) of 28.509 fg/mL, effectively differentiating HER-2 expression in various cell lines and distinguishing HER-2 levels in serum samples from healthy individuals and breast cancer patients. Its adaptability to electrochemical workstations, microplate readers, and smartphones makes it ideal for point-of-care testing (POCT), reinforcing its potential as a powerful tool for drug mechanism studies and breast cancer diagnosis.