Self-Assembly Sugar Derivative-Linked Nucleic Acid Nanoparticle for Nucleic Acid Medicine Delivery

DNA- or RNA-based nucleic acid structures (NASs) have garnered significant interest as potential carriers for nucleic acid medicine delivery due to their ability to create unique sequence-based structures. However, for the biological application of NASs, it is still challenging to create a nanostructure that is stable and avoidance of recognition as an immunogenicity under physiological conditions.<br/>We have developed a novel type of NAS called RION (reversibly ionic oligonucleotide-based nanoparticles including microRNAs) through a self-assembly process involving RNA-RNA hybridization and electrostatic interactions facilitated by chemically modified oppositely charged ion oligo nucleic acids[Miyamoto N., et al., <i>Advanced therapeutics</i> 2023, 6, 2200265]. In this research, to demonstrate the versatility of the chemical modification of RION, we designed a sugar derivative linked to RIONs. The sugar derivative-linked RION nanoparticles exhibit a spherical shape with a diameter of less than 100 nm, as observed in transmission electron microscopy images. Moreover, we found that sugar derivative-linked RION, when loaded with tumor suppressor microRNA, effectively inhibits the growth of human colorectal cancer cells (DLD-1 cells) in a dose-dependent manner. On the other hand, the sugar derivative-linked RION demonstrated transfection efficiency in a floating cancer cell line, a well-known difficult transfection with commercialized Lipofection regents. This report introduces RION technology as an innovative platform for delivering nucleic acid-based medicines, offering promising potential for applications in the field of cancer therapy and beyond.