An All-in-One DNA Nanodevice as a Programmed Theranostic Platform for Intelligent Cancer Cell Identification and On-Site Drug Release

Chemotherapy remains the cornerstone of malignant tumor treatment; however, off-target effects and severe systemic toxicity limit its efficacy. Here, we developed a programmable theranostic platform based on an all-in-one smart DNA nanodevice (SND) that integrates a programmable cancer-cell classifier (PCC) with a responsive delivery system (RDS). By employing a modular design that permits the customization of aptamer combinations for specific cancer cell types, the platform achieves accurate tumor recognition and spatially controlled drug release. Functioning as a dual-aptamer molecular guide, the PCC utilizes an interlocked configuration to identify cell-surface biomarkers in a stepwise manner, thereby ensuring highly specific target cell recognition. The RDS is constructed from a 1D central trunk flanked by double-stranded drug-loading units, a structure that confers high payload capacity and nuclease-enhanced resistance. These peripheral units also function as recognition elements for endogenous stimuli; upon activation, they trigger conformational changes that facilitate efficient intracellular drug release. In vivo studies in tumor-bearing mice demonstrate that this programmable theranostic platform selectively accumulates in tumor tissues, leading to marked inhibition of tumor growth and a substantial reduction in systemic toxicity. By integrating programmable molecular recognition with stimulus-responsive drug delivery, our theranostic platform offers a promising strategy for advancing targeted cancer therapy.