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

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.

Combining Gold Nanoparticles with Other Radiosensitizing Agents for Unlocking the Full Potential of Cancer Radiotherapy.

About half of cancer patients (50%) receive radiotherapy (RT) for the treatment of local tumors. However, one of the main obstacles in RT is the close proximity of adjacent organs at risk, resulting in treatment doses being limited by significant tissue toxicity, hence preventing the necessary dose escalation that would guarantee local control. Effective local cancer therapy is needed to avoid progression of tumors and to decrease the development of systemic metastases which may further increase the possibility of resection. In an effort to do so, radiosensitizing agents are introduced to further increase damage to the tumor while minimizing normal tissue toxicity. Cisplatin and docetaxel (DTX) are currently being used as radiation dose enhancers in RT. Recent research shows the potential of gold nanoparticles (GNPs) as a radiosensitizing agent. GNPs are biocompatible and have been tested in phase I clinical trials. The focus will be on exploring the effects of adding other radiosensitizing agents such as DTX and cisplatin to the GNP-RT platform. Therefore, a combined use of local radiosensitizing agents, such as GNPs, with currently available radiosensitizing drugs could make a significant impact in future RT. The ultimate goal is to develop treatments that have limited or nonexistent side effects to improve the quality of life of all cancer patients.