Targeting F2R/PAR1 with ligand decorated lipid nanocarriers for enhanced drug delivery into ovarian cancer cells

TL;DR

This paper describes a new method of delivering chemotherapy drugs to ovarian cancer cells using targeted lipid nanoparticles, which may reduce side effects and improve treatment effectiveness.

Contribution

The study introduces a novel ligand-decorated lipid nanoparticle system for targeted drug delivery to ovarian cancer cells via the F2R/PAR1 receptor.

Findings

Peptide-conjugated lipid nanoparticles showed significantly increased cellular uptake in ovarian cancer cells.

The targeted nanoparticles demonstrated enhanced cytotoxicity compared to non-conjugated nanoparticles.

F2R/PAR1 is validated as a promising cell surface target for drug delivery in ovarian cancer.

Abstract

Ovarian cancer treatment by chemotherapy is often complicated by severe systemic toxicity, highlighting the need for targeted delivery techniques that can improve drug efficacy while minimizing off-target effects. Our previous research identified the G protein-coupled receptor (GPCR), coagulation factor II thrombin receptor/protease activated receptor 1 (F2R/PAR1), as a potential therapeutic target in metastatic ovarian cancer tissues. Here we report the design of an engineered lipid nanoparticle (LNP), conjugated with a synthetic short peptide agonist that mimics the F2R-activating tethered ligand. Doxorubicin (DOX)-loaded LNPs (LNP-DOX), were physically characterized to assess the drug encapsulation efficacy, particle size, polydispersity index (PDI), zeta potential, and release kinetics. In vitro investigation demonstrated that the peptide-conjugated LNPs had significantly increased cellular uptake and cytotoxicity compared to their non-conjugated equivalents in an established ovarian cancer cell line. The results underscore the therapeutic potential of ligand-directed nanocarriers for targeted drug delivery into ovarian cancer cells and further validates F2R as a promising cell surface target.

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