Work

An effective tumor-inhibiting siRNA delivery platform

Year: 2026

Type: article

Abstract: 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. • -NRP-1 targeted polyplex effectively delivered siRNA to triple-negative breast cancer xenografts. • -siRaf-1 and siPD-L1 polyplex markedly reduced tumor size by 75% and 82%, respectively. • -The reduced tumor size was based on enhanced apoptosis and decreased cell division. • -No toxicity to normal tissues was observed with the polyplex.

Source: Biochemical and Biophysical Research Communications

DOI: 10.1016/j.bbrc.2026.153430

Authors: Qixin Leng, A. James Mixson

Institution: University of Maryland, Baltimore

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,110