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金纳米颗粒增强质子束辐射下细胞在扩展布拉格峰处活性氧的产生

Gold-Nanoparticles-Enhanced Production of Reactive Oxygen Species in Cells at Spread-Out Bragg Peak under Proton Beam Radiation.

作者信息

Lo Chang-Yun, Tsai Shiao-Wen, Niu Huan, Chen Fang-Hsin, Hwang Hsiao-Chien, Chao Tsi-Chian, Hsiao Ing-Tsung, Liaw Jiunn-Woei

机构信息

Department of Mechanical Engineering, Chang Gung University, Taoyuan 333, Taiwan.

Department of Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

ACS Omega. 2023 May 9;8(20):17922-17931. doi: 10.1021/acsomega.3c01025. eCollection 2023 May 23.

DOI:10.1021/acsomega.3c01025
PMID:37251180
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10210040/
Abstract

This study investigates the radiobiological effects of gold nanoparticles (GNPs) as radiosensitizers for proton beam therapy (PBT). Specifically, we explore the enhanced production of reactive oxygen species (ROS) in GNP-loaded tumor cells irradiated by a 230 MeV proton beam in a spread-out Bragg peak (SOBP) zone obtained by a passive scattering system. Our findings indicate that the radiosensitization enhancement factor is 1.24 at 30% cell survival fraction, 8 days after 6 Gy proton beam irradiation. Since protons deposit the majority of their energy at the SOBP region and interact with GNPs to induce more ejected electrons from the high-Z GNPs, these ejected electrons then react with water molecules to produce excessive ROS that can damage cellular organelles. Laser scanning confocal microscopy reveals the excessive ROS induced inside the GNP-loaded cells immediately after proton irradiation. Furthermore, the damage to cytoskeletons and mitochondrial dysfunction in GNP-loaded cells caused by the induced ROS becomes significantly severe, 48 h after proton irradiation. Our biological evidence suggests that the cytotoxicity of GNP-enhanced ROS production has the potential to increase the tumoricidal efficacy of PBT.

摘要

本研究调查了金纳米颗粒（GNPs）作为质子束疗法（PBT）放射增敏剂的放射生物学效应。具体而言，我们探究了在通过被动散射系统获得的扩展布拉格峰（SOBP）区域中，由230 MeV质子束照射负载GNP的肿瘤细胞时，活性氧（ROS）生成的增强情况。我们的研究结果表明，在6 Gy质子束照射8天后，细胞存活分数为30%时，放射增敏增强因子为1.24。由于质子将其大部分能量沉积在SOBP区域，并与GNPs相互作用，从高原子序数的GNPs中诱导出更多的出射电子，这些出射电子随后与水分子反应产生过量的ROS，从而损害细胞器。激光扫描共聚焦显微镜显示，质子照射后立即在负载GNP的细胞内诱导产生了过量的ROS。此外，质子照射48小时后，由诱导产生的ROS对负载GNP的细胞造成的细胞骨架损伤和线粒体功能障碍变得明显严重。我们的生物学证据表明，GNP增强ROS生成的细胞毒性有可能提高PBT的杀肿瘤疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/e67c7f29fe39/ao3c01025_0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/c646ae78f116/ao3c01025_0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/1770a9d8dcf4/ao3c01025_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/db6113331d88/ao3c01025_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/4fe4a1dfcdb2/ao3c01025_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/ae119f632834/ao3c01025_0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/868c4f3e28a0/ao3c01025_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/c0ca676ecb33/ao3c01025_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/3f0d0c87240a/ao3c01025_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/e67c7f29fe39/ao3c01025_0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/c646ae78f116/ao3c01025_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/36d478a729f3/ao3c01025_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/1770a9d8dcf4/ao3c01025_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/db6113331d88/ao3c01025_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/4fe4a1dfcdb2/ao3c01025_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/ae119f632834/ao3c01025_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/a12c80353729/ao3c01025_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/f589f7011470/ao3c01025_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/868c4f3e28a0/ao3c01025_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/c0ca676ecb33/ao3c01025_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/3f0d0c87240a/ao3c01025_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ae/10210040/e67c7f29fe39/ao3c01025_0013.jpg

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[5]
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本文引用的文献

[1]
Gold Nanoparticles Enhancing Generation of ROS for Cs-137 Radiotherapy.

Nanoscale Res Lett. 2022-12-14

[2]
Proton induced DNA double strand breaks at the Bragg peak: Evidence of enhanced LET effect.

Front Oncol. 2022-8-5

[3]
Moderately Hypofractionated Proton Beam Therapy for Locally Advanced Non-Small Cell Lung Cancer: A New Way Forward for Dose Escalation?

Int J Radiat Oncol Biol Phys. 2022-7-15

[4]
Comparing Geant4 physics models for proton-induced dose deposition and radiolysis enhancement from a gold nanoparticle.

Sci Rep. 2022-2-2

[5]
Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams.

Biochem Biophys Res Commun. 2021-12-31

[6]
Radiosensitization Effect of Gold Nanoparticles in Proton Therapy.

Front Public Health. 2021

[7]
Biological Effective Dose for Treatment of a Heterogeneous Population of Cells with a Spread-Out Bragg Peak of Particle Radiation.

Radiat Res. 2021-10-1

[8]
Proton Beam Therapy for Local Recurrence of Rectal Cancer.

Anticancer Res. 2021-7

[9]
High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak.

Front Oncol. 2021-6-10

[10]
Physical and Biological Characteristics of Particle Therapy for Oncologists.

Cancer Res Treat. 2021-7

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