Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

Abstract

Pancreatic cancer is one of the deadliest types of cancer, with a five-year survival rate of only 10%. Nanotechnology offers a novel perspective to treat such deadly cancers through their incorporation into radiotherapy and chemotherapy. However, the interaction of nanoparticles (NPs) with cancer cells and with other major cell types within the pancreatic tumor microenvironment (TME) is yet to be understood. Therefore, our goal is to shed light on the dynamics of NPs within a TME of pancreatic origin. In addition to cancer cells, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were examined in this study due to their important yet opposite roles of suppressing tumor growth and promoting tumor growth, respectively. Gold nanoparticles were used as the model NP system due to their biocompatibility and physical and chemical proprieties, and their dynamics were studied both quantitatively and qualitatively in vitro and in vivo. The in vitro studies revealed that both cancer cells and CAFs take up 50% more NPs compared to NFs. Most importantly, they all managed to retain 70–80% of NPs over a 24-h time period. Uptake and retention of NPs within an in vivo environment was also consistent with in vitro results. This study shows the paradigm-changing potential of NPs to combat the disease.

Docetaxel-Mediated Uptake and Retention of Gold Nanoparticles in Tumor Cells and in Cancer-Associated Fibroblasts

“…We believe that the NP concentration within MIA PaCa-2 was higher; however, they responded faster to the concentration gradient, resulting in a lower number of NPs within them at the end. Overall, the extent of the decrease in NP retention in tumor cells could be due to a combination of exocytosis dynamics and redistribution of NPs via cell division [43]. We found no correlation between the cell division time and the percent retention among the different tumor cells.…”

Gold Nanoparticles Uptake in Monoculture vs Co-culture of Pancreatic Cancer Cells

“…No significant difference was found between the average uptake of FITC-labelled GNPs in MiaPaca2 and CAF98 when they are in monoculture vs when they are in co-culture. However, the uptake of GNPs in CAFs is much higher than that of tumour cells in both monoculture and co-culture, which is in agreement with our previous experiments that were done in monoculture [16][17]. This is an important observation that might open the door for targeting both tumour cells and CAFs using GNPs.…”

“…1A. The former was added to simulate an in vivo environment in which PEG would help nanoparticles avoid the immune system, and the latter was added to improve the nanoparticles' uptake into cancer cells [16][17]. GNPs shape and size were verified using Transmission Electron Microscopy (TEM), Fig.…”

“…Nanoparticles of high-Z materials such as gold nanoparticles (GNPs) have shown promising results as radiosensitizer agents in radiotherapy and as vectors for targeted-drug delivery in chemotherapy [4][5]12]. There is also tremendous evidence that GNPs and low concentrations of anticancer drugs can sensitize cancer cells to radiotherapy in monoculture in vitro environment [13][14][15][16][17]. In monoculture, CAFs have shown to uptake more GNPs into them when compared to cancer cells [16][17].…”

“…There is also tremendous evidence that GNPs and low concentrations of anticancer drugs can sensitize cancer cells to radiotherapy in monoculture in vitro environment [13][14][15][16][17]. In monoculture, CAFs have shown to uptake more GNPs into them when compared to cancer cells [16][17]. However, real-life tumour environments exist in co-culture and not in monocultures.…”