Supramolecular Bioconjugation Strategy for Antibody-Targeted Delivery of siRNA

Area of Science:

• Biotechnology
• Molecular Biology
• Nanomedicine

Background:

• RNA interference (RNAi) is a biological process for sequence-specific gene silencing via mRNA targeting.
• The physicochemical properties of small interfering RNAs (siRNAs) pose significant delivery challenges, limiting bioavailability.
• Targeted delivery of therapeutic agents to cancer cells remains a critical unmet need.

Purpose of the Study:

• To develop a novel, selective siRNA delivery system for HER2-overexpressing cancer cells.
• To utilize a trastuzumab-conjugated nanocarrier for targeted delivery of siRNA.
• To evaluate the efficiency of gene silencing induced by the developed delivery system.

Main Methods:

• Development of immunoconjugates through electrostatic interactions between oligonucleotide-modified antibodies and cationic micelles.
• Assembly of supramolecular nanocarriers for siRNA encapsulation.
• In vitro assessment of gene silencing efficacy targeting luciferase and PLK-1 in HER2-overexpressing cancer cells.

Main Results:

• The trastuzumab-conjugated nanocarrier system successfully encapsulated siRNA.
• The nanocarrier system demonstrated efficient and cell-selective gene silencing of luciferase and PLK-1 in vitro.
• Optimal siRNA loading at a specific N/P ratio was crucial for efficient gene silencing.

Conclusions:

• Trastuzumab-conjugated nanocarriers represent a versatile and selective platform for siRNA delivery.
• This targeted delivery approach shows promise for HER2-overexpressing cancer therapy.
• The developed system overcomes key challenges in siRNA delivery and bioavailability.