Pancreatic cancer is one of the deadliest with a 5-year survival of 6 to 9%. Nanotechnology offers paradigm-changing opportunity to treat such cancers. Successful integration of nanotechnology into the current paradigm of cancer therapy requires proper understanding of the interface between nanoparticles (NPs) and cancer cells, as well as other key components within the tumor microenvironment (TME), such as normal fibroblasts (FBs) and cancer-associated FBs (CAFs). So far, much focus has been on cancer cells, but FBs and CAFs also play a critical role: FBs suppress the tumor growth while CAFs promote it. It is not yet known how NPs interact with FBs and CAFs compared to cancer cells. Hence, our goal was to elucidate the extent of NP uptake and retention in cancer cells, FBs, and CAFs of pancreatic origin to further understand the fate of NPs in a real tumor-like environment. We used gold nanoparticles as our model NP system due to their numerous applications in cancer therapy, including radiotherapy and chemotherapy. Our NP uptake studies revealed that both cancer cells and CAFs take up 50% more NPs compared to NFs. We also looked at the potential of NP retention. Cancer cells and CAFs were still managed retain between 70 to 80% of NPs over a 24 hour time period. Higher uptake and retention of NPs in cancer cells and CAFs vs FBs is very important in promoting NP-based applications in cancer therapy. Our results show potential in modulating uptake and retention of GNPs among key components of TME, in an effort to develop NP-based strategies to suppress the tumor growth. An ideal NP-based platform would eradicate tumor cells, protect FBs, and deactivate CAFs. Therefore, this study lays a road map to exploit the TME for the advancement of “smart” nanomedicines that would constitute the next generation of cancer therapeutics to treat pancreatic cancer.
High atomic number nanomaterials have been explored as a tool for improving cancer therapeutics. Gold nanoparticles are a system that has been introduced as they can act as effective radiation dose enhancers and anticancer drug carries. Gold nanoparticles have unique physiochemical properties that allow them to be probed in cells using techniques such as scanning electron microscopy and hyper spectral imaging. Optimization of gold nanoparticle uptake into 3D in-vitro models is essential to optimizing future cancer therapeutic applications and bridging the gap between in-vitro and in-vivo tumor environments. The uptake of functionalized gold nanoparticles into 2D monolayer and 3D spheroid cell models was tested. Functionalization of the GNPs was confirmed by use of dynamic light scattering, UV-Visible light spectroscopy, the Zeta potential, and imaged with a scanning electron microscope and hyper spectral imaging. These findings suggest that both the size and functionalization of the gold nanoparticles should be considered in future 3D in-vitro studies.
Recent developments in nanotechnology has provided new tools for cancer therapy and diagnosis. Among other nanomaterial systems, gold nanoparticles are being used as radiation dose enhancers and anticancer drug carriers in cancer therapy. Fate of gold nanoparticles within biological tissues can be probed using techniques such as TEM (transmission electron microscopy) and SEM (Scanning Electron Microscopy) due to their high electron density. We have shown for the first time that cancer drug loaded gold nanoparticles can reach the nucleus (or the brain) of cancer cells enhancing the therapeutic effect dramatically. Nucleus of the cancer cells are the most desirable target in cancer therapy. In chemotherapy, smart delivery of highly toxic anticancer drugs through packaging using nanoparticles will reduce the side effects and improve the quality and care of cancer patients. In radiation therapy, use of gold nanoparticles as radiation dose enhancer is very promising due to enhanced localized dose within the cancer tissue. Recent advancement in nanomaterial characterization techniques will facilitate mapping of nanomaterial distribution within biological specimens to correlate the radiobiological effects due to treatment. Hence, gold nanoparticle mediated combined chemoradiation would provide promising tools to achieve personalized and tailored cancer treatments in the near future.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.