Intelligent DNA\nNanosystem for Broad-Spectrum Oncological\nTyping and Therapy

The\noccurrence of multiple primary cancers in individual\npatients\nunderscores the need for diagnostic and therapeutic techniques with\naugmented cancer-targeting selectivity and broad-spectrum antitumor\neffects. To address this, we develop a quadruple-input-triggered <u>O</u>R-<u>A</u>ND-<u>A</u>ND logic gated oncological nanosystem (OAA). This system employs\nfour cancer-related markers (EpCAM, MUC1, APE1, and miR-21) to generate\nthree distinct fluorescence signals, enabling precise differentiation\nof various cancer cell lines (MCF-7, HepG2, and HeLa) from normal\ncells (MCF-10A). Additionally, the OAA system integrates photodynamic\ntherapy (PDT) and gene silencing strategies, allowing selective activation\nof Ce6 release, miR-21 gene silencing, and VEGFR2 mRNA gene silencing\nthrough the OR-AND-AND logic gating mechanism in a cancer-specific\nmanner. This synergetic therapeutic approach induces significant apoptosis\nin multiple cancer cell lines while sparing normal cells, demonstrating\nimproved cancer-targeting specificity and broad-spectrum versatility.\nThis intelligent platform precisely types and treats diverse cancer\ncells, powering the future exploration of advanced diagnostic and\ntherapeutic strategies to combat highly heterogeneous diseases.