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Updated: Feb 17, 2026

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An effective tumor-inhibiting siRNA delivery platform.

Qixin Leng1, A James Mixson1

  • 1Department of Pathology, University of Maryland School of Medicine, University of Maryland Baltimore, 10 S. Pine St., Baltimore, MD, 21201, USA.

Biochemical and Biophysical Research Communications
|February 15, 2026
PubMed
Summary

This study shows histidine-lysine (HK) peptide polyplexes effectively deliver siRNA to triple-negative breast cancer cells. The system significantly reduced tumor size by targeting Raf-1 and PD-L1 oncogenes.

Keywords:
Breast cancerHistidineLysineNeuropilin-1PD-L1PeptidePolyplexRaf-1siRNA

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Area of Science:

  • Biotechnology
  • Oncology
  • Molecular Biology

Background:

  • Histidine-lysine (HK) peptides can deliver siRNA, targeting tumor-specific receptors like Neuropilin-1 (NRP-1).
  • NRP-1 is overexpressed in aggressive tumors, including triple-negative breast cancer (TNBC).

Purpose of the Study:

  • To evaluate the antitumor efficacy of an HK peptide-siRNA delivery system against TNBC.
  • To assess the targeting of oncogenes Raf-1 and PD-L1 using this system in vivo.

Main Methods:

  • Systemic delivery of HK peptide polyplexes carrying siRaf-1 or siPD-L1 to MDA-MB-231 tumor-bearing athymic mice.
  • Tumor size measurement and protein level analysis (Raf-1, PD-L1) post-treatment.
  • Monitoring of animal weight as an indicator of systemic toxicity.

Main Results:

  • siRaf-1 and siPD-L1 polyplexes reduced tumor volume by 75% and 82%, respectively, compared to siControl.
  • Tumor size reduction correlated with decreased Raf-1 and PD-L1 protein expression.
  • No significant weight loss was observed in treated groups, indicating good tolerability.

Conclusions:

  • HK peptide polyplexes are a promising platform for targeted siRNA delivery in TNBC.
  • This system demonstrates significant antitumor activity and warrants further clinical development.
  • Targeting oncogenes like Raf-1 and PD-L1 with siRNA offers a viable therapeutic strategy.