Abstract

Gold nanoparticles (GNPs) have been shown to be effective contrast agents for imaging and emerge as powerful radiosensitizers, constituting a promising theranostic agent for cancer. Although the radiosensitization effect was initially attributed to a physical mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of oxidative stress in this process. This work evidences the central role played by thioredoxin reductase (TrxR) in the GNP-induced radiosensitization. A cell type-dependent reduction in TrxR activity was measured in five different cell lines incubated with GNPs leading to differences in cell response to X-ray irradiation. Correlation analyses demonstrated that GNP uptake and TrxR activity inhibition are associated to a GNP radiosensitization effect. Finally, Kaplan-Meier analyses suggested that high TrxR expression is correlated to low patient survival in four different types of cancer. Altogether, these results enable a better understanding of the GNP radiosensitization mechanism, which remains a mandatory step towards further use in clinic. Moreover, they highlight the potential application of this new treatment in a personalized medicine context.
Original languageEnglish
Pages (from-to)295
Number of pages13
JournalNanomaterials
Volume9
Issue number2
DOIs
Publication statusPublished - 2019

Fingerprint

Thioredoxin-Disulfide Reductase
Gold
Nanoparticles
Precision Medicine
Kaplan-Meier Estimate
Contrast Media
Neoplasms
Oxidative Stress
X-Rays
Cell Line
Survival

Keywords

  • gold nanoparticles
  • radiosensitization
  • thioredoxin reductase
  • radiation
  • prognosis
  • biochemical mechanism

Cite this

@article{447e095461514c2f96485a326995a490,
title = "Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect",
abstract = "Gold nanoparticles (GNPs) have been shown to be effective contrast agents for imaging and emerge as powerful radiosensitizers, constituting a promising theranostic agent for cancer. Although the radiosensitization effect was initially attributed to a physical mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of oxidative stress in this process. This work evidences the central role played by thioredoxin reductase (TrxR) in the GNP-induced radiosensitization. A cell type-dependent reduction in TrxR activity was measured in five different cell lines incubated with GNPs leading to differences in cell response to X-ray irradiation. Correlation analyses demonstrated that GNP uptake and TrxR activity inhibition are associated to a GNP radiosensitization effect. Finally, Kaplan-Meier analyses suggested that high TrxR expression is correlated to low patient survival in four different types of cancer. Altogether, these results enable a better understanding of the GNP radiosensitization mechanism, which remains a mandatory step towards further use in clinic. Moreover, they highlight the potential application of this new treatment in a personalized medicine context.",
keywords = "gold nanoparticles, radiosensitization, thioredoxin reductase, radiation, prognosis, biochemical mechanism",
author = "S{\'e}bastien Penninckx and Anne-Catherine Heuskin and Carine Michiels and St{\'e}phane Lucas",
year = "2019",
doi = "10.3390/nano9020295",
language = "English",
volume = "9",
pages = "295",
journal = "Nanomaterials",
issn = "2079-4991",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
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}

TY - JOUR

T1 - Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect

AU - Penninckx, Sébastien

AU - Heuskin, Anne-Catherine

AU - Michiels, Carine

AU - Lucas, Stéphane

PY - 2019

Y1 - 2019

N2 - Gold nanoparticles (GNPs) have been shown to be effective contrast agents for imaging and emerge as powerful radiosensitizers, constituting a promising theranostic agent for cancer. Although the radiosensitization effect was initially attributed to a physical mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of oxidative stress in this process. This work evidences the central role played by thioredoxin reductase (TrxR) in the GNP-induced radiosensitization. A cell type-dependent reduction in TrxR activity was measured in five different cell lines incubated with GNPs leading to differences in cell response to X-ray irradiation. Correlation analyses demonstrated that GNP uptake and TrxR activity inhibition are associated to a GNP radiosensitization effect. Finally, Kaplan-Meier analyses suggested that high TrxR expression is correlated to low patient survival in four different types of cancer. Altogether, these results enable a better understanding of the GNP radiosensitization mechanism, which remains a mandatory step towards further use in clinic. Moreover, they highlight the potential application of this new treatment in a personalized medicine context.

AB - Gold nanoparticles (GNPs) have been shown to be effective contrast agents for imaging and emerge as powerful radiosensitizers, constituting a promising theranostic agent for cancer. Although the radiosensitization effect was initially attributed to a physical mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of oxidative stress in this process. This work evidences the central role played by thioredoxin reductase (TrxR) in the GNP-induced radiosensitization. A cell type-dependent reduction in TrxR activity was measured in five different cell lines incubated with GNPs leading to differences in cell response to X-ray irradiation. Correlation analyses demonstrated that GNP uptake and TrxR activity inhibition are associated to a GNP radiosensitization effect. Finally, Kaplan-Meier analyses suggested that high TrxR expression is correlated to low patient survival in four different types of cancer. Altogether, these results enable a better understanding of the GNP radiosensitization mechanism, which remains a mandatory step towards further use in clinic. Moreover, they highlight the potential application of this new treatment in a personalized medicine context.

KW - gold nanoparticles

KW - radiosensitization

KW - thioredoxin reductase

KW - radiation

KW - prognosis

KW - biochemical mechanism

U2 - 10.3390/nano9020295

DO - 10.3390/nano9020295

M3 - Article

VL - 9

SP - 295

JO - Nanomaterials

JF - Nanomaterials

SN - 2079-4991

IS - 2

ER -