# 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.

## Key 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.