Jeong Eun Ju, Choi Moonhwan, Lee Jangwook, Rhim Taiyoun, Lee Kuen Yong
Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
Nanoscale. 2015 Dec 21;7(47):20095-104. doi: 10.1039/c5nr06903c. Epub 2015 Nov 16.
Although chitosan and its derivatives have been frequently utilized as delivery vehicles for small interfering RNA (siRNA), it is challenging to improve the gene silencing efficiency of chitosan-based nanoparticles. In this study, we hypothesized that controlling the spacer arm length between a cell-penetrating peptide (CPP) and a nanoparticle could be critical to enhancing the cellular uptake as well as the gene silencing efficiency of conventional chitosan/siRNA nanoparticles. A peptide consisting of nine arginine units (R9) was used as a CPP, and the spacer arm length was controlled by varying the number of glycine units between the peptide (R9Gn) and the nanoparticle (n = 0, 4, and 10). Various physicochemical characteristics of R9Gn-chitosan/siRNA nanoparticles were investigated in vitro. Increasing the spacing arm length did not significantly affect the complex formation between R9Gn-chitosan and siRNA. However, R9G10-chitosan was much more effective in delivering genes both in vitro and in vivo compared with non-modified chitosan (without the peptide) and R9-chitosan (without the spacer arm). Chitosan derivatives modified with oligoarginine containing a spacer arm can be considered as potential delivery vehicles for various genes.
尽管壳聚糖及其衍生物经常被用作小分子干扰RNA（siRNA）的递送载体，但提高基于壳聚糖的纳米颗粒的基因沉默效率仍具有挑战性。在本研究中，我们假设控制细胞穿透肽（CPP）与纳米颗粒之间的间隔臂长度对于提高传统壳聚糖/siRNA纳米颗粒的细胞摄取以及基因沉默效率可能至关重要。由九个精氨酸单元（R9）组成的肽被用作CPP，通过改变肽（R9Gn）与纳米颗粒之间甘氨酸单元的数量来控制间隔臂长度（n = 0、4和10）。在体外研究了R9Gn-壳聚糖/siRNA纳米颗粒的各种物理化学特性。增加间隔臂长度对R9Gn-壳聚糖与siRNA之间的复合物形成没有显著影响。然而，与未修饰的壳聚糖（不含肽）和R9-壳聚糖（无间隔臂）相比，R9G10-壳聚糖在体外和体内递送基因方面都更有效。含有间隔臂的寡聚精氨酸修饰的壳聚糖衍生物可被视为各种基因的潜在递送载体。
