Intelligent DNA Nanosystem for Broad-Spectrum Oncological Typing and Therapy.

The occurrence of multiple primary cancers in individual patients underscores the need for diagnostic and therapeutic techniques with augmented cancer-targeting selectivity and broad-spectrum antitumor effects. To address this, we develop a quadruple-input-triggered R-ND-ND logic gated oncological nanosystem (OAA). This system employs four cancer-related markers (EpCAM, MUC1, APE1, and miR-21) to generate three distinct fluorescence signals, enabling precise differentiation of various cancer cell lines (MCF-7, HepG2, and HeLa) from normal cells (MCF-10A). Additionally, the OAA system integrates photodynamic therapy (PDT) and gene silencing strategies, allowing selective activation of Ce6 release, miR-21 gene silencing, and VEGFR2 mRNA gene silencing through the OR-AND-AND logic gating mechanism in a cancer-specific manner. This synergetic therapeutic approach induces significant apoptosis in multiple cancer cell lines while sparing normal cells, demonstrating improved cancer-targeting specificity and broad-spectrum versatility. This intelligent platform precisely types and treats diverse cancer cells, powering the future exploration of advanced diagnostic and therapeutic strategies to combat highly heterogeneous diseases.