Polyvalent Nucleic Acid Nanoprobes for Cancer Diagnosis and Therapy

Nucleic acids, as essential biomacromolecules, have garnered considerable scientific interest in diagnosis and therapy owing to their unique molecular characteristics, including sequence-specific programmability, precise molecular recognition capabilities, and diverse biological functionalities. In recent years, with the deepening of the understanding of the physicochemical properties of nucleic acids and the development of nanotechnology, nucleic acid-based nanoprobes with sophisticated structures and functions have been gradually developed, opening up a new direction for efficient diagnosis, followed by customized therapy for diseases. Despite the progress, the affinity and stability of nucleic acids to target sites still suffer from severe challenges, especially in complex physiological environments. Polyvalent nucleic acids, integrated with different functional elements, have demonstrated enormous advantages in effectively solving the above limitations by the elaborate design and construction of multifunctional DNA nanostructures, making them promising candidates for smart-responsive nanoprobes. In this review, we commence with an exploration of nucleic acids, subsequently delineating state-of-the-art strategies for the fabrication of polyvalent nucleic acid nanostructures. We then predominantly underscore the latest advancements in these nanostructures as innovative platforms for cancer theranostics. Further, we critically examine the biomedical applications of polyvalent nucleic acids, alongside addressing the prevailing challenges and future prospects in the realm of nucleic acid-facilitated diagnostics and therapeutics.