Nanotechnology Driven Cancer Chemoradiation: Exploiting the Full Potential of Radiotherapy with a Unique Combination of Gold Nanoparticles and Bleomycin.

Ocean Han,Wayne Beckham,Mesa Monica,Alexandre G Brolo,Ariadne T Bido,Perry L Howard,Abraham S Alexander,Kyle Bromma,Abdulaziz Alhussan,Nicholas Palmerley,Devika B Chithrani

doi:10.3390/pharmaceutics14020233

Ocean Han, Wayne Beckham + Show 9 more

Open Access

https://doi.org/10.3390/pharmaceutics14020233

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Abstract

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.

Highlights

According to current statistics, more than half of cancer patients receive radiotherapy (RT), and, in some cases, RT is the only treatment option [1,2]
Gold nanoparticles (GNPs) 10–15 nm in diameter were synthesized with the citrate reduction method: 1.18 mL of 1% tetra chloroauric acid (HAuCl4 ) was brought to a boil in 28.82 mL of ddH2 O before adding 1.2 mL of 5% sodium citrate tribasic dihydrate (HOC(COONa)(CH2 COONa)2 ·2H2 O)
The bright specs in the darkfield image are from gold nanoparticles (GNPs), which were further verified by taking a spectral map across the same area using the hyperspectral feature of the same microscope

Summary

Introduction

More than half of cancer patients receive radiotherapy (RT), and, in some cases, RT is the only treatment option [1,2]. RT is an integral component of the curative-intent treatment of many tumors. In RT, high doses of radiation are used to kill cancer cells and shrink tumors via direct and indirect mechanisms [1]. Enhancing the effect of RT has tremendous potential to maximize the dose to the tumor while mitigating damage to surrounding normal tissue [3,4]. Both of these issues are being addressed using nanotechnology [5,6].

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