Recent Advances in Tetrahedral Framework Nucleic Acids for Multimodal Synergistic Cancer Therapy

ABSTRACT The complexity, heterogeneity, and evolution of tumors have driven a shift in the paradigm of treatment from monotherapy to multimodal synergistic therapy. Tetrahedral framework nucleic acids (tFNAs) have garnered substantial attention for their potential to construct synergistic therapy nanoplatforms owing to their precise programmability, inherent biological functions, and excellent biocompatibility. In this review, we systematically discuss the latest advances in tFNA‐based multimodal cancer therapy. We begin by introducing the structural characteristics and drug‐delivery strategies of tFNAs, focusing on innovative tFNA‐based bimodal and multimodal synergistic therapeutic regimens aiming to address key challenges in cancer treatment, such as multidrug resistance (MDR), tumor hypoxia, and immunosuppression. Finally, we systematically summarize general design principles for tFNA‐based multimodal therapy and analyze the core obstacles hindering its translational progress. Notably, the combination of intelligent response mechanisms and immune regulation functions emerges as a highly promising research direction, and the critical scientific and technological bottlenecks for its clinical application are also emphasized herein.