Fluorinated polymers in gene delivery

Cationic polymers were widely used as non-viral gene carriers, however, the transfection efficacy and cytotoxicity of these polymers are strongly associated with each other, that is high transfection efficacy is usually accompanied by serious toxicity. How to prepare polymeric carriers with high transfection efficacy and low toxicity is a key challenge in clinical gene therapy. Fluorinated polymers are a new class of non-viral gene carriers with interesting physicochemical properties. Fluoroalkyl substances have unique properties compared to traditional alkyl lipids. They are both hydrophobic and lipophobic, but prefer to associate with other fluorous compounds via a fluorophilic effect. As a result, fluorinated polymers with low critical aggregation concentrations can efficiently condense nucleic acids into stable complexes at an extremely low nitrogen to phosphorous ratio or polymer dose. Fluorous ligands such as fluoroalkyls are beneficial for improved serum stability, cellular uptake, endosomal escape, and intracellular nucleic acid release, endowing the fluorinated polymers with a specific fluorous effect in gene delivery. The fluorinated polymers possess excellent self-assembly property and combine the features of cationic polymers and liposomes in gene delivery, for example, the high tissue penetration capability of cationic polymers, and self-assembly behavior and high gene transfection efficacy of cationic liposomes. The self-assembled fluoropolymers show excellent serum resistance due to the bioinert property of fluoroalkyl chains. They exhibit high gene transfection efficacy even in medium containing 50% serum, and thus present promising potential for clinical gene therapy. Compared to traditional alkylated materials, fluorinated polymers show more efficient cellular internalization and less toxicity due to reduced intermolecular interactions with the phospholipids in cell membrane. This feature article summarized recent advances of fluorinated polymers in gene delivery. The transfection efficacy and mechanism of fluorinated polymers in gene delivery, as well as their applications in gene therapy and gene editing were discussed. Finally, future perspectives of fluorinated polymers in gene delivery, protein and peptide delivery and other biomedical fields were given.