One of the major issues in current radiotherapy (RT) is the associated normal tissue toxicity. Enhancement of the RT effect with novel radiosensitizers can address this need. In this study, gold nanoparticles (GNPs) and bleomycin (BLM) were used as a unique combination of radiosensitizers. GNPs offer a two-fold promise as a delivery vehicle for BLM and as a radiosensitizing agent. In this study, GNPs were functionalized and complexed with BLM using a gold-thiol bond (denoted GNP-BLM). Our results show that there was a 40% and 10% decrease in cell growth with GNP-BLM vs. free BLM for the MIA PaCa-2 and PC-3 cell lines, respectively. Testing the GNP-BLM platform with RT showed an 84% and 13% reduction in cell growth in MIA PaCa-2 cells treated with GNP-BLM and GNPs, respectively. Similar results were seen with PC-3 cells. The efficacy of this approach was verified by mapping DNA double-strand breaks (DSBs) as well. Therefore, this proposed incorporation of nanomedicine with RT is promising in achieving a significantly higher therapeutic ratio which is necessary to make a paradigm change to the current clinical approach.
Only a small fraction of anticancer drugs gets (<0.01%) into the tumor when they are administered as free drugs to cancer patients. This results in many side effects to patients since drug molecules get into healthy, normal cells as well as tumour cells. We propose using gold nanoparticles (GNPs) for controlled and optimized delivery of drugs to overcome the side effects of poor distribution of anticancer drugs. Our studies show that normal cells take much less GNPs in contrast to tumor cells making them a more selective delivery vehicle for anticancer drugs. In this study, we have shown that GNPs offer the possibility of transporting major quantities of drugs due to their large surface-to-volume ratio. We have functionalized GNPs with natural peptides and polyethylene glycol for effective intracellular targeting and biocompatibility, respectively. In this in vitro study, we chose to use bleomycin (BLM) as the anticancer drug due to its limited therapeutic efficiency (harmful side effects). BLM was conjugated onto GNPs through a thiol bond. The effectiveness of BLM was observed by visualizing DNA double strand breaks and by calculating the survival fraction. The action of the drug (where the drug takes effect) is known to be in the nucleus, and our experiments have shown that some of the GNPs carrying BLM were present in the nucleus. The use of GNPs to deliver anticancer drugs increased the delivery and therapeutic efficacy compared to the free drug. Combined use of radiation therapy and chemotherapy is being used to treat locally advanced tumors. It is shown that GNPs can also be used as radiation dose enhancers. Therefore, this GNP-based drug carrier will make a paradigm change in achieving a significantly higher therapeutic ratio while minimizing side effects of both chemotherapy and radiotherapy while improving the quality of life of cancer patients.
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