Logic‐Gated DNA Production Line for Cancer Cell Recognition and Intracellular Cascaded Gene Therapy

Tumor-derived biomarkers can precisely reflect cell types, offering major potential for early detection and therapy. An engineered platform capable of distinguishing various biomarkers for cancer type identification and autonomous responsive therapeutics is urgently needed. Herein, a "one stop" production line with logic gated composite for tumor cell identification, related biomarker imaging, and subsequent gene therapy is proposed. The designed composite can specifically target cancer cells through incorporated aptamers, which endows it with identification preference for cancer cells with overexpressed membrane protein receptors. Internalized materials collapse in the acidic lysosome milieu, releasing the functioning DNA strands. Endogenous miR-210 then can initiate cascade reactions with released strands, resulting in the liberation of therapeutic antisense oligonucleotides (ASO). The strategy is to construct a platform for cancer therapy based on second-order AND Boolean logic operation for multiple cancer biomarkers (Mucin 1 (MUC1), Protein tyrosine kinase 7 (PTK7), and miR-210) identification and succeeding therapy toward identified cells. Through the logic operation, produced fluorescent signals can disclose the types of biomarkers being recognized, while nano-material endocytosis, subsequent miRNA imaging, and endogenous miRNA-triggered gene therapy can all be performed concurrently. This "one stop" multifunctional production line demonstrates excellent sensitivity and accuracy, and presents promising prospects in the early diagnosis of tumors and precision medicine.