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

Abdulaziz Alhussan,Daniel J Renouf,Devika B Chithrani,Joanna Karasinska,Wayne Beckham,Ece Pinar Demirci Bozdoğan,Andrew Metcalfe,Abraham S Alexander,Kyle Bromma,David F Schaeffer

doi:10.3390/curroncol28030183

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.

Highlights

IntroductionThe current human lifetime risk of developing cancer is about 40%, and the risk of dying from it is about 21% [1]
gold nanoparticles (GNPs) were used as our model NP system since they have been successfully tested as radiosensitizers and drug carriers in radiotherapy and chemotherapy, respectively [23]
Unfunctionalized GNPs naturally bind to plasma proteins at their surface, enabling their cellular uptake into the cell [24]. This makes them vulnerable to attacks from the immune system which clears them from the system, causing GNPs to have a short bloodstream circulation lifetime [25]

Summary

Introduction

The current human lifetime risk of developing cancer is about 40%, and the risk of dying from it is about 21% [1]. Its treatment regimens are highly dependent on the cancer stage and location, and include surgery, chemotherapy, and radiation therapy [2,3,4,5]. Despite the advances in radiation therapy, chemotherapy, and surgical procedures in the last decade, pancreatic cancer is still one of the least survivable of all cancer types, with a five-year death rate of 90% [2,3,4,5]. One of the major issues in radiotherapy (RT) in treating pancreatic cancer is the close proximity of adjacent organs at risk, resulting in treatment doses being limited by significant tissues’

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