Currently, gene therapy is considered a potentially universal approach to the treatment of a wide range of diseases, such as cancer, cardiovascular diseases, diabetes, inherited diseases, and many others. It is known that “naked” nucleic acid is not able to effectively overcome the extra- and intracellular barriers to reach the target cell since it is easily degraded. In this regard, it becomes necessary to create special delivery vehicles. We investigated the modular arginine-rich cysteine-flanked polycondensed carriers stabilized by anionic glutamic acid-rich peptides. Glutamic acid-rich peptides can give colloidal stability to the studied complexes and protect them from interaction with negatively charged components of blood serum.

Physicochemical, toxic, and transfection properties of the investigated complexes with siRNA were studied in cancer cell line MDA-MB-231-GFP⁺. Condensation analysis showed that the complexes with optimal charge ratios are not destroyed by the addition of anionic peptides. Also, these polyplexes were stable in the serum-containing culture medium during cell transfection and non-toxic for the cells. Moreover, we measured the average size and zeta-potential of the siRNA-nucleopeptide complexes. Based on this study, it was concluded that the complexes are capable of stably bind siRNA and have a high transfection efficiency in an optimal charge ratio, which provides new opportunities for the use of these carriers for siRNA delivery in vivo.