Tetrahedral framework nucleic acids as an advanced drug delivery system for oligonucleotide drugs

• Main Authors: Yuhao Liu, Zhiqiang Liu, Weitong Cui, Yanjing Li, Xin Qin, Mei Zhang, Yunfeng Lin
• Format: Article
• Language: English
• Published: AIP Publishing LLC 2020-10-01
• Series: APL Materials
• Online Access: http://dx.doi.org/10.1063/5.0025211

Nucleic acid therapy has played a promising role in the treatment of many diseases, such as cancer, infections, immune diseases, and neurodegenerative diseases. However, its application is still limited mainly because of poor cell-entry performance and low resistance to in vivo degradation. Tetrahedral framework nucleic acids (tFNAs) have shown potential in delivering low-molecular-weight drugs owing to their stability, biocompatibility, cell-entry performance, and flexible drug-loading ability. In particular, tFNAs can successfully deliver oligonucleotide drugs with improved effects and co-deliver oligonucleotide drugs with other drugs for synergistic effects. In this review, the recent progress on tFNA-based delivery of oligonucleotide drugs is outlined by single delivery systems—through sequence extension and complementation, and co-delivery systems—through multiple sequence extension, drug–DNA interactions, and specific binding. Furthermore, the current limitations and future developments of tFNA-based delivery of oligonucleotide drugs are discussed.