Multifunctional Tandem Peptide Mediates Targeted siRNA Delivery to Ovarian Cancer Cells

Area of Science:

• Biotechnology
• Molecular Biology
• Cancer Research

Background:

• Fusogenic peptides improve nucleic acid delivery, protecting against degradation and aiding endosomal escape.
• Systemic delivery of nucleic acids using fusogenic peptides requires refinement for targeted applications.
• Active targeting strategies enhance cell- and tissue-specific delivery, minimizing off-target effects.

Purpose of the Study:

• To develop a targeted fusogenic peptide, LHRHR-DIV3W, for enhanced delivery to ovarian cancer cells.
• To investigate the peptide's ability to target the luteinizing hormone-releasing hormone receptor (LHRHR), which is overexpressed in ovarian cancer.
• To evaluate the efficacy of the tandem peptide in delivering small interfering RNAs (siRNAs) for gene silencing.

Main Methods:

• Synthesis and characterization of the LHRHR-DIV3W tandem peptide.
• Formation of monodisperse peptide-siRNA nanocomplexes and assessment of their stability.
• In vitro studies involving receptor-specific internalization in ovarian cancer cell lines.
• Evaluation of gene silencing efficacy of siRNA targeting the oncogene CSNK2A1.

Main Results:

• LHRHR-DIV3W formed stable, monodisperse nanocomplexes protecting siRNA in physiological conditions.
• Peptide-siRNA nanocomplexes showed specific internalization in LHRHR-expressing ovarian cancer cells.
• Combined fusogenic and targeting sequences in the tandem peptide increased siRNA internalization by 40% compared to targeting peptide alone.
• Significant silencing of the oncogene CSNK2A1 was achieved in OVCAR3 ovarian cancer cells.

Conclusions:

• A tandem peptide combining cell-targeting and membrane-disruptive functions serves as an effective platform for nucleic acid therapy delivery.
• Targeted delivery systems utilizing peptides like LHRHR-DIV3W can enhance specificity and efficacy in cancer treatment.
• This approach holds promise for developing advanced nucleic acid-based therapies for ovarian cancer and potentially other malignancies.