Abstract B23: Bioadhesive nanoparticles as a delivery vehicle in pancreatic cancer epithelial cells and pancreatic fibroblasts

Abstract

Abstract Pancreatic cancer, referred to as pancreatic ductal adenocarcinoma (PDAC), is characterized by high lethality and limited treatment options. PDAC is generally diagnosed at a later stage and is resistant to chemotherapy and radiation therapy. Therefore, there is an urgent unmet need for novel treatment options to improve the survival of patients. PDAC is characterized by dense solid tumors that hinder drug penetration, and novel treatment technologies should be utilized to improve drug access to cancer cells. Nanoparticle-based compounds have been shown to improve site specific targeting, intracellular penetration, and circulation time and therefore can be used for therapeutic delivery to solid tumors. In our study, we performed in vitro characterization studies of non-bioadhesive nanoparticles (NNPs) and bioadhesive nanoparticles (BNPs) in pancreatic cancer epithelial cells and pancreatic fibroblasts. NNPs are polylactic acid-hyperbranched polyglycerol (PLA-HPG) nanoparticles and BNPs are obtained through conversion of HPG to an aldehyde-rich corona, which increases the bioadhesive property through formation of linkages with proteins. The aim of our study was to characterize the internalization of nanoparticles in vitro in different pancreatic cell lines. We incubated pancreatic cancer epithelial cells (PANC-1 and MIA PaCa-2) and pancreatic fibroblasts with fluorescent DiO-loaded NNPs and BNPs to assess internalization. Both DiO-NNPs and DiO-BNPs were internalized by PANC-1, MIA PaCa-2, and pancreatic fibroblasts as determined by both flow cytometry and fluorescence microscopy. The nanoparticles were internalized in a dose- and treatment time-dependent manner. Although both nanoparticles were internalized, due to their increased bioadhesive properties BNPs had 1.7-fold higher internalization compared to NNPs. Viability of the cells following DiO-NNPs and DiO-BNPs treatment was assessed through both acridine orange staining and flow cytometry analysis. DiO-NNPs and DiO-BNPs treatments did not affect the viability of the cells. Similar results were obtained with DiI-loaded nanoparticles. In summary, our study shows that nanoparticles can be internalized by pancreatic cancer epithelial cells and pancreatic fibroblasts and do not cause any loss of viability. Our results demonstrate the potential applicability of nanoparticles, especially bioadhesive nanoparticles, for synergistic therapeutic targeting of different cell types in pancreatic cancer to improve treatment outcomes. Citation Format: Nesrin M. Hasan, Hee Won Suh, Mark Saltzman, Nita Ahuja. Bioadhesive nanoparticles as a delivery vehicle in pancreatic cancer epithelial cells and pancreatic fibroblasts [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B23.