Coordination-induced gold nanoparticle assembly for smartphone-enabled detection of KAT5 activity in circulating...

Lysine acetyltransferase 5 (KAT5) plays a critical role in epigenetic regulation and is closely associated with the progression of various cancers, particularly hepatocellular carcinoma. However, convenient and portable methods for monitoring KAT5 activity remain limited. Herein, we report a coordination-regulated colorimetric sensing platform based on the localized surface plasmon resonance of gold nanoparticles (AuNPs) for KAT5 activity detection. In this strategy, Zn²⁺ coordinates with ethylenediamine (en) to form Zn(en)₂²⁺ complexes, which induce AuNPs aggregation and a distinct plasmonic color change. In the presence of coenzyme A (CoA), generated during the KAT5-catalyzed acetylation reaction, Zn²⁺ preferentially binds to thiol-containing CoA, suppressing Zn(en)₂²⁺ formation and inhibiting AuNPs aggregation. As a result, KAT5 activity is indirectly converted into a measurable colorimetric signal with a detection limit of 1.9 pg/mL (3σ/slope). To enable portable analysis, smartphone-based image processing was integrated, using the blue-to-red (B/R) ratio for quantification. The platform was further applied to investigate histone acetylation in cancer cells and circulating tumor cell (CTCs)-like models during epithelial-mesenchymal transition, revealing dynamic changes in KAT5 activity. This coordination-mediated AuNPs strategy provides a simple and portable tool for monitoring cancer-related enzymatic activity, with potential applications in liquid biopsy, early cancer diagnosis, and precision medicine.