Progress of Framework Nucleic Acids in Tumor Diagnosis and Therapy.
INTRODUCTION Framework Nucleic Acids (FNAs) are precisely self-assembled two- or three-dimensional nucleic acid architectures renowned for their excellent programmability, monodisperse structures, and near-atomic precision. These distinctive properties enable FNAs to function as versatile nanocarriers for targeted biomarker recognition, efficient co-delivery of therapeutics and imaging agents, and stimuli-responsive release within the tumor microenvironment, driving rapid advances in framework nucleic acid-based nanomaterials for tumor theranostics in recent years. METHODS We extensively searched bibliographic databases using keywords such as "framework nucleic acids", "FNA", "DNA nanostructures," and "tumor theranostics". Based on the literature retrieved, we summarized the design and functionalization strategies of FNA-based nanomaterials, reviewed their applications in various tumor therapeutic modalities, and discussed the major challenges for clinical translation. RESULTS FNAs exhibited excellent application prospects across diverse tumor therapeutic modalities. They markedly enhanced targeted drug delivery and therapeutic efficacy in chemotherapy, enabled efficient gene silencing in gene therapy, strengthened antitumor immune responses in immunotherapy, and significantly improved precision in tumor imaging and phototherapy. Collectively, these advantages position FNAs as a highly promising and versatile platform for precision tumor theranostics. DISCUSSION We have further provided a comprehensive discussion of the multifaceted challenges that continue to impede the clinical translation of Framework Nucleic Acid (FNA)-based nanomaterials despite their considerable preclinical promise in tumor theranostics, as well as an in-depth outlook on their future potential in this evolving field. CONCLUSION This review summarizes the remarkable potential of Framework Nucleic Acids (FNAs) as an intelligent nanoplatform for tumor diagnosis and therapy. Nevertheless, several critical challenges persist for clinical translation, including long-term biosafety, scalable manufacturing, and efficient in vivo delivery. Future efforts to address these barriers are expected to accelerate the clinical implementation of FNAs in precision oncology.