Photoexcited Electro‐Driven Reactive Oxygen Species Channeling for Precise Extraction of Biomarker Information from Tumor Interstitial Fluid

Direct electrochemical detection of miRNA biomarkers in tumor tissue interstitial fluid (TIF) holds great promise for adjuvant therapy for tumors in the perioperative period, yet is limited by background interference and weak signal. Herein, a wash-free and separation-free miRNA biosensor based on photoexcited electro-driven reactive oxygen channeling analysis (LEOCA) is developed to solve the high-fidelity detection in physiological samples. In the presence of miRNA, nanoacceptors (ultrasmall-size polydopamine, uPDA) are responsively assembled on the surface of nanodonors (zirconium metal-organic framework, ZrMOF) to form core-satellite aggregates. The produced lifetime-constraint singlet oxygen upon light irradiation is captured by the catechol of constrained uPDA, and the oxidized quinone is immediately electro-reduced to the catechol at transient collision process on the electrode, resulting in a cascade electron transfer and amplified current. Thereby, the nanosensor exhibits a low detection limit (1.1 fM), and high reproducibility (relative standard deviation of 2.0%). Compared with quantitative real-time polymerase chain reaction (qRT-PCR), the clinical accuracy (area under the curve value) is significantly increased from 0.75 to 0.93 in distinguishing breast cancer patients from healthy donors. This study demonstrates an inspiration on the synergy of the reactive oxygen channeling between nanodonor/nanoacceptor and the synchronous electron transfer cascade on the electrode to solve the bottleneck problem of detecting unprocessed clinical samples in a sample-in-answer-out manner.