Cytotoxic effects and specific gene expression alterations induced by I-125-labeled triplex-forming oligonucleotides

Dahmen, Volker; Kriehuber, Ralf

doi:10.3109/09553002.2012.702298

Cited by 13 publications

(3 citation statements)

References 26 publications

(38 reference statements)

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“…On the other hand, the radiosensitizing mechanism operating through DNA damage could be more efficient. A solution of this dilemma could be based on selective targeting of nanoparticles to specific genome sequences, like oncogenes, using appropriately designed oligo-nucleotides as being available for radio-emitters [70]. With techniques of COMBO-FISH [71,72] and PNA probe combinations [73], NPs may be transferred to cell nuclei and specifically addressed to given chromatin targets.…”

Section: Discussionmentioning

confidence: 99%

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Pagáčová

Štefančíková

Schmidt-Kaler

et al. 2019

IJMS

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From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns.

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Section: Discussionmentioning

confidence: 99%

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Pagáčová

Štefančíková

Schmidt-Kaler

et al. 2019

IJMS

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“…An additional option that has been explored for targeting of cancer cell DNA is the use of triplex forming oligonucleotides (TFO), site-specific molecules that bind to the major groove of duplex DNA to form a triplex helix. Several studies by Dahmen and Kriehuber (2012) and Dahmen et al (2016 , 2017 ) have demonstrated that TFOs can be readily labeled with radionuclides, such as 125 I and 111 In, and that these conjugates can exert site- and sequence-specific DNA damage in cancer cells.…”

Section: Subcellular Targets For Radionuclide Therapymentioning

confidence: 99%

Subcellular Targeting of Theranostic Radionuclides

et al. 2018

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The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging rely on a radiolabeled vector to specifically target cancer cells. Radionuclides that emit β particles have thus far dominated the field of targeted radionuclide therapy (TRT), mainly because the longer range (μm–mm track length) of these particles offsets the heterogeneous expression of the molecular target. Shorter range (nm–μm track length) α- and Auger electron (AE)-emitting radionuclides on the other hand provide high ionization densities at the site of decay which could overcome much of the toxicity associated with β-emitters. Given that there is a growing body of evidence that other sensitive sites besides the DNA, such as the cell membrane and mitochondria, could be critical targets in TRT, improved techniques in detecting the subcellular distribution of these radionuclides are necessary, especially since many β-emitting radionuclides also emit AE. The successful development of TRT agents capable of homing to targets with subcellular precision demands the parallel development of quantitative assays for evaluation of spatial distribution of radionuclides in the nm–μm range. In this review, the status of research directed at subcellular targeting of radionuclide theranostics and the methods for imaging and quantification of radionuclide localization at the nanoscale are described.

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“…Another type of DNA targeting agent are the radiolabelled forms of major groove‐binding triplex‐forming oligonucleotides (TFO), which interact with specific DNA sequences. Dahmen et al used 125 I‐labelled TFOs against various DNA sequences such as GAPDH or multi‐binding site . They showed selective induction of DNA damage, selective reduction of target gene expression and reduction of clonogenic survival in vitro .…”

Section: Therapy With a Focus On Intranuclear And Dna Targetingmentioning

confidence: 99%

Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

Cornelissen

2014

Labelled Comp Radiopharmac

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Molecular imaging of tumour tissue focusses mainly on extracellular epitopes such as tumour angiogenesis or signal transduction receptors expressed on the cell membrane. However, most biological processes that define tumour phenotype occur within the cell. In this mini-review, an overview is given of the various techniques to interrogate intracellular events using molecular imaging with radiolabelled compounds. Additionally, similar targeting techniques can be employed for radionuclide therapy using Auger electron emitters, and recent advances in Auger electron therapy are discussed.

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Cytotoxic effects and specific gene expression alterations induced by I-125-labeled triplex-forming oligonucleotides

Cited by 13 publications

References 26 publications

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Subcellular Targeting of Theranostic Radionuclides

Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

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