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Optimization of PEG coated nanoscale gold particles for enhanced radiation therapy

机译：PEG涂层纳米级金颗粒优化增强辐射治疗

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摘要

Nanoscale gold particles are being used as a radiation dose enhancer in cancer research. The purpose of this study was to optimize the uptake of polyethylene glycol (PEG) functionalized gold nanoparticles (GNPs) for an enhanced therapeutic effect during radiation therapy. PEG is widely used in providing NPs with stealth properties, thus prolonging blood circulation times. However, PEG minimizes PEG-GNP interaction with cell surface ligands resulting in significantly lower in vitro cellular uptake. As intracellular localization of GNPs maximizes its therapeutic enhancement, there is a need to improve the uptake of PEG-GNPs. To enhance uptake, RGD peptide containing an integrin binding domain was conjugated along with PEG. Spherical GNPs of diameters 14 and 50 nm and PEG chain lengths of 2 kDa were used for the study. Nanoparticles functionalized with both RGD peptide and PEG had higher uptake than NPs functionalized with PEG alone. The enhancement in uptake was higher for 14 nm NPs as compared to 50 nm NPs. Our radiation therapy results showed that smaller NPs conjugated with PEG and RGD peptides have a three-fold therapeutic enhancement as compared to larger NPs in MDA-MB-231 cells at clinically relevant 6 MV energy. This study will shed light on clinical use of GNPs in radiation therapy in the near future.
机译：纳米级金颗粒被用作癌症研究中的辐射剂量增强剂。本研究的目的是优化聚乙二醇（PEG）官能化金纳米颗粒（GNPS）的摄取，以提高放射治疗期间的治疗效果。 PEG广泛用于提供具有隐形性质的NPS，从而延长血液循环时间。然而，PEG使PEG-GNP与细胞表面配体相互作用最小化，导致体外细胞摄取的显着降低。随着GNP的细胞内定位最大化其治疗增强，需要改善PEG-GNP的吸收。为了增强摄取，将含有整合蛋白结合结构域的RGD肽与PEG一起缀合。直径14和50nm的球形GNP和2kDa的PEG链长度用于该研究。用RGD肽和PEG官能化的纳米颗粒具有比单独用PEG官能化的NPS更高的摄取。与50 nm的NP相比，吸收的增强较高为14nm。我们的放射治疗结果表明，与PEG和RGD肽缀合的较小NPS具有三倍的治疗增强，与临床相关的6mV能量的MDA-MB-231细胞中的较大NPS相比。本研究将在不久的将来揭示GNPS在放射治疗中的临床应用。

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  • 来源
    《RSC Advances》 |2015年第123期|共8页
  • 作者

    Cruje C.; Yang C.; Uertz J.; van Prooijen M.; Chithrani B. D.;

  • 作者单位

    Ryerson Univ Dept Phys Toronto ON M5B 2K3 Canada;

    Ryerson Univ Dept Phys Toronto ON M5B 2K3 Canada;

    CytoViva Inc Auburn AL 36832 USA;

    Princess Margaret Canc Ctr Toronto ON M5G 2M9 Canada;

    Ryerson Univ Dept Phys Toronto ON M5B 2K3 Canada;

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  • 正文语种 eng
  • 中图分类 化学;
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