Dual Zn2+/Cu2+ Chelation-Engineered Nanotherapeutics for DNA-Mitochondrial Disruption in TNBC

Trace metal dysregulation, particularly Zn²⁺ and Cu²⁺ overload, drives oncogenic signaling in triple negative breast cancer (TNBC). We pioneer a dual-chelation strategy targeting zinc-copper homeostasis to amplify photodynamic therapy (PDT): Zn²⁺ chelation triggers histone hyperacetylation-mediated chromatin relaxation, sensitizing nuclear DNA damage, while Cu²⁺ deprivation disrupts mitochondrial electron transport. This nanotherapeutics synergistically induce concurrent DNA double-strand breaks and mitochondrial dysfunction, eliciting catastrophic apoptosis.