Han Ocean, Bromma Kyle, Palmerley Nicholas, Bido Ariadne T, Monica Mesa, Alhussan Abdulaziz, Howard Perry L, Brolo Alexandre G, Beckham Wayne, Alexander Abraham S, Chithrani Devika B
Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada.
Department of Chemistry, University of Victoria, Victoria, BC V8P 5C2, Canada.
Pharmaceutics. 2022 Jan 20;14(2):233. doi: 10.3390/pharmaceutics14020233.
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.
当前放射治疗(RT)的主要问题之一是相关的正常组织毒性。使用新型放射增敏剂增强放疗效果可以满足这一需求。在本研究中,金纳米颗粒(GNPs)和博来霉素(BLM)被用作一种独特的放射增敏剂组合。GNPs作为BLM的递送载体和放射增敏剂有双重前景。在本研究中,通过金硫醇键将GNPs功能化并与BLM复合(表示为GNP-BLM)。我们的结果表明,对于MIA PaCa-2和PC-3细胞系,与游离BLM相比,GNP-BLM处理后的细胞生长分别降低了40%和10%。用RT测试GNP-BLM平台显示,用GNP-BLM和GNPs处理的MIA PaCa-2细胞的细胞生长分别减少了84%和13%。PC-3细胞也得到了类似的结果。通过绘制DNA双链断裂(DSBs)图谱也验证了该方法的有效性。因此,这种将纳米医学与放疗相结合的方法有望实现显著更高的治疗比,这对于改变当前临床治疗方法的范式是必要的。