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

Abstract

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.

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

“…However, it is not yet known how DTX affects NP uptake and transportation in CAFs, which play a major role in tumor progression. As DTX is a clinically approved drug that treats many cancers and acts as a complementary radiosensitizing agent in chemotherapy, understanding the role of DTX on GNP transportation could pave the way for a better chemoradiation approach with GNPs as a radiosensitizing agent [19]. Taxol-based anticancer drugs are used to treat prostate and pancreatic cancer [19].…”

“…One of the advantages of using GNPs in cancer nanomedicine is its dual ability to act as a drug carrier and a radiation dose enhancer [19]. The ability of cells to retain GNPs over an extended period of time would enable exploiting the full therapeutic potential in their applications in nanomedicine.…”

“…As most studies have mainly focused on tumor cells, our study is designed to elucidate the NP interactions in tumor cells and in CAFs. We used gold nanoparticles (GNPs) as our model NP system, since they can be used as a radiation dose enhancer in radiotherapy and a drug carrier in chemotherapy [15][16][17][18][19]. The biocompatibility of GNPs has been determined in a phase I clinical trial [20].…”

“…Recent studies have shown the promise of combining a commonly used chemotherapeutic: DTX with GNPs [21]. DTX stabilizes microtubules within the cells, arresting them in the most radiosensitive phases of the cell cycle, G2/M [19,21]. Furthermore, the presence of DTX results in an increase in the accumulation of NPs within tumor cells, making it very promising in both chemotherapy and radiotherapy.…”

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

“…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]. The optimization of GNP physical properties (size, shape, surface properties, etc.)…”