Khalil Ikramy A, Kogure Kentaro, Futaki Shiroh, Harashima Hideyoshi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido, Japan.
Int J Pharm. 2008 Apr 16;354(1-2):39-48. doi: 10.1016/j.ijpharm.2007.12.003. Epub 2007 Dec 14.
Gene therapy is a promising new approach for treating a variety of genetic and acquired diseases. While viral vectors are highly efficient for gene therapy, their use is associated with high toxicity and immunogenicity. Synthetic or nonviral vectors are attractive alternatives to viral vectors because of their low immunogenicity and low acute toxicity. The main disadvantage of the nonviral vectors is the low transfection efficiency compared to viral vectors. Novel functional devices to enhance the transfection activities of nonviral vectors are needed. In this review, we discuss the modification of liposomal drug carriers with a novel functional device, the octaarginine (R8) peptide, for drug and gene delivery. Decoration of liposomes with R8 enhanced their cellular uptake. In addition, by optimizing the density of the peptide as well as its topology, the liposomes could be internalized via clathrin-independent pathways, which improved the intracellular trafficking through avoiding lysosomal degradation. A special emphasis is given to the need for optimizing the conditions of using the peptide to not only enhance the cellular uptake but also to improve the intracellular trafficking of its cargos. In addition, the use of R8-modified liposomes and nano-particles in gene delivery is discussed.
基因治疗是一种治疗多种遗传性和后天性疾病的很有前景的新方法。虽然病毒载体在基因治疗中效率很高，但其使用与高毒性和免疫原性相关。合成或非病毒载体因其低免疫原性和低急性毒性而成为病毒载体有吸引力的替代品。非病毒载体的主要缺点是与病毒载体相比转染效率低。需要新型功能性装置来提高非病毒载体的转染活性。在这篇综述中，我们讨论了用一种新型功能性装置八聚精氨酸（R8）肽修饰脂质体药物载体用于药物和基因递送的情况。用R8修饰脂质体增强了它们的细胞摄取。此外，通过优化肽的密度及其拓扑结构，脂质体可以通过不依赖网格蛋白的途径内化，这通过避免溶酶体降解改善了细胞内运输。特别强调了优化使用该肽的条件的必要性，这不仅可以增强细胞摄取，还可以改善其货物的细胞内运输。此外，还讨论了R8修饰的脂质体和纳米颗粒在基因递送中的应用。
