An effective tumor-inhibiting siRNA delivery platform.

We recently found that combining two histidine-lysine (HK) peptides effectively delivered siRNA and silenced their tumor targets. One HK peptide stabilized the siRNA within the polyplex, while the other primarily targeted the NRP-1 receptor. This receptor is often overexpressed in tumors, particularly aggressive ones. In this study, we investigated the antitumor efficacy of this delivery system against the triple-negative breast cancer cell line MDA-MB-231. These cells express high levels of NRP-1, making them a suitable model for this approach. Two tumor-promoting oncogenes, Raf-1 or PD-L1, were targeted with the systemically delivered HK peptide polyplex in an athymic mouse model. The siRaf-1 and siPD-L1 polyplexes reduced tumor size by 75% and 82%, respectively, compared with the siControl polyplex. The size reduction of these tumors, achieved through siRNA therapy, was confirmed by decreased levels of Raf-1 and PD-L1 proteins. We observed no weight differences between the therapeutic and untreated groups. These promising results should encourage further development of siRNA therapy with this carrier platform.