Pärnaste Ly, Arukuusk Piret, Langel Kent, Tenson Tanel, Langel Ülo
Institute of Technology, University of Tartu, Nooruse 1-517, 50411 Tartu, Estonia.
Institute of Technology, University of Tartu, Nooruse 1-517, 50411 Tartu, Estonia.
Mol Ther Nucleic Acids. 2017 Jun 16;7:1-10. doi: 10.1016/j.omtn.2017.02.003. Epub 2017 Feb 10.
Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation. We conclude that the pH dependent change of the net charge of the CPP may very well be the key factor leading to the high delivery efficiency and the optimal binding strength between CPPs to siRNAs, while the hydrophobicity, secondary structure of the CPP, and the positions of the positive charges are responsible for the stability of the CPP/siRNA particles. Also, CPPs with distinct hydrophobic and hydrophilic regions may assemble into nanoparticles that could be described as core-shell formulations.
细胞穿透肽（CPPs）是广泛用于协助生物活性物质运输至细胞内靶点的递送载体。这些物质包括细胞无法自然内化的小干扰RNA（siRNA）。阐明CPP与物质复合物形成背后的复杂性对于理解与其递送相关的过程至关重要。在本研究中，我们使用了CPP转运蛋白10的修饰类似物，并研究了这些CPP与siRNA的结合特性、CPP/siRNA复合物的形成参数及其对酶降解的稳定性。我们得出结论，CPP净电荷的pH依赖性变化很可能是导致高递送效率以及CPP与siRNA之间最佳结合强度的关键因素，而CPP的疏水性、二级结构和正电荷位置则决定了CPP/siRNA颗粒的稳定性。此外，具有不同疏水和亲水区域的CPP可能组装成可描述为核壳制剂的纳米颗粒。
