The effect of cell penetrating peptides on transfection activity and cytotoxicity of polyallylamine

Introduction: Cationic polymers have the potential to be modified to achieve an ideal gene vector lacking viral vector defects. The aim of the present study was to improve polyallylamine (PAA) transfection efficiency and to reduce cytotoxicity by incorporating of cell-penetrating peptides (CPPs). Methods: To prepare the peptide-based polyplexes, PAA (15 kDa) was modified with 2 peptides (TAT and CyLoP-1) by covering the 0.5% and 1% of amines. Buffer capacity and DNA condensation ability of modified polymer, particle size and zeta potential of nanoparticles, cell viability, and transfection activity of vectors were evaluated. Results: In low carrier to plasmid (C/P) weight ratios such as 0.5 and 1, the unmodified polymer was more capable to condense the DNA compared to the synthesized vectors. In C/P ratio of 2, the plasmid was fully condensed in all vectors. The size of polyplexes ranged from 195 to 240 nm. The zeta potential was almost as the same as PAA and varied from 25 to 27 mV. All polyplexes increased the buffer capacity compared to PAA. The transfection efficiency was improved compared to unmodified polymer especially in the vectors modified with 1% of TAT or CyLoP-1 peptides in C/P ratio of 2. The cytotoxicity of prepared vectors was less than PAA. In most ratios, the cytotoxicity of the CyLoP-1 modified samples was less than the TAT modified ones. Conclusion: Modification of PAA with CPPs improved the transfection activity of vector