Abstract
Nucleic acid drugs have a strong therapeutic potential for treatment of many intractable diseases, including cancer. However, their bioavailability seems to be miserable owing to their high susceptibility to enzymatic degradation and negatively charged macromolecular structures that hamper their cellular entry. To overcome these bottlenecks, a variety of delivery vehicles, such as ligand-nucleotide conjugates, lipid nanoparticles, and polymeric nanoparticles, have been developed for successful nucleotide therapeutics. This article describes the design strategies of synthetic block copolymer-based nucleic acid delivery systems, particularly highlighting "smart" polyion complex (PIC) micelles that can exert the desired functions in response to biological microenvironment signals. Also, our recent results related to small interfering RNA (siRNA) and messenger RNA delivery are introduced with details. Notably, the ligand-installed PIC micelle has achieved efficient tumor-targeted siRNA delivery through systemic route, leading to the significant antitumor activity in subcutaneous tumor models.
