Interfacial Stabilization of Cu(I) in Ultralow-Dose Cu₂O/ZIF-8 Heterojunctions Enabling Rapid and Energy-Efficient Genomic Disruption of Pathogens

Achieving rapid and genetic photocatalytic inactivation of pathogens under low-energy conditions remains a critical, yet unresolved challenge. Herein, we developed a Cu₂O/ZIF-8 heterojunction catalyst that requires only 5 μg mL^–1to achieve complete pathogenic inactivation within 15 min under irradiation from a 13 W light-emitting diode source. Physicochemical characterizations and theoretical calculations reveal that the Fermi-level equilibration at the heterointerface facilitates the stabilization of Cu(I) via the formation of an interfacial electron-rich region. This electronic modulation, coupled with efficient photoinduced charge carrier separation across the heterojunction, significantly enhances the generation of^•O₂^–. Abundant^•O₂^–species disrupt cell membranes, compromise membrane permeability, and induce DNA fragmentation. Transcriptomic analysis shows that beyond morphological damage, the photocatalytic process induces widespread changes in gene expression across diverse biological processes, cellular components, and molecular functions. Pathway enrichment analyses further reveal upregulation of genes associated with the negative regulation of genetic material and DNA repair, alongside downregulation of genes involved in amino acid biosynthesis. This transcriptional reprogramming suppresses critical regulatory networks governing nucleic acid and protein metabolism, ultimately leading to the irreversible genetic inactivation of pathogens. Overall, this work provides a promising energy-efficient strategy for rapid and thorough pathogen inactivation along with mechanistic insights at the genetic level.