Cell-penetrating peptides for siRNA delivery to glioblastomas.

Delivery of small interfering RNA (siRNA) to suppress glioblastoma growth is a hurdle due to the critical obstacles of the blood-brain barrier and the siRNA properties of such as high negative charges and instability in serum. Therefore, the passage of siRNA to targeted cells is limited. Several siRNA carriers have been constructed using cell-penetrating peptides (CPPs) since the CPPs have shown a high potential for oligonucleotide delivery into the cells. In this study, two CPPs, PepFect 14 (PF14) and the amphipathic peptide PepFect 28 (PF28), were modified with targeting peptides by covalent conjugation and non-covalent complex formation to improve glioma-targeted specificity and gene-silencing efficiency. In conclusion, we have established an efficient non-covalently complexed carrier (PF14:TG1) for siRNA delivery to human glioblastoma cells (U87), showing a significant two-fold increase in gene-silencing efficiency compared to the parent peptide PF14 and also improved specificity to U87 cells compared to non-glioma targeted cells.