Hierarchical DNA Octahedral Nanoplatform for in Situ Biosensing and Clinical Monitoring of Acute Lymphoblastic Leukemia

Abstract Developing nanoscale platforms with high integration, assembly efficiency, and structural stability for performing complex computations in specific cells remains a significant challenge. To address this, the Three‐dimensional Hierarchical Octahedral Robotic (THOR) DNA nanoplatform is introduced, which integrates targeting, logic computation, and sensing modules within a single framework. This nanoplatform specifically binds to cancer cell surface proteins, releasing aptamer‐linked fuel chains to initiate subsequent computational processes. Three logic gates efficiently compute any arbitrary binary combination of target proteins. The sensing module employs catalytic hairpin assembly for detecting specific miRNAs with high sensitivity. THOR demonstrates robust functionality both in vitro and in situ. As a proof‐of‐concept, this nanoplatform to distinguish acute lymphoblastic leukemia (ALL) patients from other leukemia subtypes and healthy participants, achieving 100% accuracy is applied. Additionally, this approach reliably monitored the therapeutic progress of ALL patients, showing strong concordance with bone marrow smear results. The THOR platform highlights the feasibility of constructing a reliable, hierarchical, and multifunctional analytical system based on a single DNA polyhedron. It offers a promising auxiliary tool for clinical diagnostics and therapeutic monitoring.