Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect.
Sébastien PenninckxAnne-Catherine HeuskinCarine MichielsStéphane LucasPublished in: Nanomaterials (Basel, Switzerland) (2019)
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.
Keyphrases
- gold nanoparticles
- oxidative stress
- papillary thyroid
- high resolution
- poor prognosis
- diabetic rats
- primary care
- physical activity
- squamous cell carcinoma
- mental health
- photodynamic therapy
- squamous cell
- mass spectrometry
- computed tomography
- case report
- mesenchymal stem cells
- magnetic resonance imaging
- risk assessment
- single cell
- fluorescence imaging
- lymph node metastasis
- radiation induced
- binding protein
- reduced graphene oxide
- combination therapy
- case control
- human health
- induced apoptosis