(28z) Modeling Nanocarrier Efficacy in a Three-Dimensional Multicellular Model of Endometrial Cancer

Endometrial cancer is the most common gynecological cancer worldwide and is the sixth most common cancer in women. There are an estimated 382,000 new cases and 90,000 deaths a year from endometrial cancer as well as rising incidence and mortality rates since the 1970s. Although surgery at early stages is typically sufficient, surgery at late stages is often followed by chemotherapy. There are currently only four unique FDA approved chemotherapies for endometrial cancer. We encapsulated paclitaxel (PTX), a powerful chemotherapeutic drug, in poly (caprolactone) (PCL) nanoparticles to increase the efficacy of PTX. Briefly, the nanoparticles were made using the solvent emulsion evaporation method where PCL and PTX were dissolved in dichloromethane and sonicated in a poly(vinyl alcohol) and water mixture. The emulsion was then stirred, and the particles were collected via centrifugation before they were lyophilized. The particles were then tested in vitro in both 2D endometrial cancer cell models (Ishikawa H, KLE, and HEC-1-A) as well as novel 3D multicellular endometrial cancer models that replicate the tumor microenvironment. The 3D model is made of multiple hydrogel layers as well as a layer of human microvascular endothelial cells (HMVEC) and a layer of endometrial cancer cells. The hydrogel layers contain a mixture of natural (collagen type I and IV, fibrinogen, fibronectin, laminin) and synthetic (GELMA, PEGDA) polymers that promotes better cell growth, micro vessel formation, and cell invasion than the gold standard Matrigel. Dose response curves were collected with both the nanoparticles as well as free PTX in both models. Confocal localization was also conducted in both the 2D and 3D models. A reduction of endometrial cancer cell growth was seen with both the nanoparticles as well as the free drug in both models.