含氟高分子基因载体

Fluorinated Polymers in Gene Delivery

阳离子高分子被广泛应用为非病毒类基因载体,但这类高分子材料的转染效率与细胞毒性之间通常存在"恶性"关联,即获得高转染效率时往往会伴随严重的细胞毒性.如何制备兼具高效、低毒特点的高分子载体是成功实施基因治疗的关键.含氟高分子是一类具有独特理化性质的高分子,能够在低电荷密度条件下与核酸形成稳定的复合物,从而实现高效、低毒的基因转染.含氟功能基团可帮助阳离子高分子改善复合物稳定性、细胞内吞、内涵体逃逸、胞内核酸释放等多个环节,从而赋予了含氟高分子在基因递送过程中的氟效应.该专论系统地总结了含氟高分子基因载体的研究,介绍了含氟高分子的基因递送性能、作用机理以及在基因治疗、基因编辑中的应用,并对含氟高分子载体的未来发展进行了展望.

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.