Therapeutic Gene Silencing Using Targeted Lipid Nanoparticles in Metastatic Ovarian Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Ovarian cancer is an aggressive malignancy known for its high metastatic potential from stage II onwards.
• Effective therapeutic strategies for advanced ovarian cancer remain a critical unmet need.

Purpose of the Study:

• To develop and evaluate novel lipid nanoparticles (LNPs) for targeted ovarian cancer therapy.
• To assess the efficacy of LNPs co-delivering small interfering RNAs (siRNAs) against PLK1 and eIF3c, modified with hyaluronan for CD44 targeting.

Main Methods:

• Generation of hyaluronan-coated LNPs (tNPs) encapsulating siRNAs targeting PLK1 and eIF3c.
• In vitro evaluation of tNPs on ovarian cancer spheroids and 2D/3D cell cultures.
• In vivo assessment in an orthotopic ovarian cancer mouse model, evaluating tumor targeting, gene silencing, and survival rates.

Main Results:

• Hyaluronan coating (tNPs) enhanced LNP activity and reduced spheroid growth compared to uncoated LNPs (uNPs) due to high CD44 expression.
• LNPs induced 85% cell death and significant gene silencing in cultured ovarian cancer cells.
• Intraperitoneal administration of tNPs demonstrated CD44-specific tumor targeting and gene silencing in vivo.
• tNP treatment resulted in a 60% overall survival rate in mice, significantly higher than control or single-siRNA groups.

Conclusions:

• Lipid nanoparticles (LNPs) represent a promising platform for advanced ovarian cancer treatment.
• Hyaluronan-functionalized LNPs enhance tumor targeting and therapeutic efficacy.
• This LNP-based siRNA delivery system improves survival rates in preclinical ovarian cancer models.