Theodossis Theodossiou

• Kalamara, A.; Stamatelatos, I. E.; Stefanopoulos, K. L. & Theodossiou, Theodossis (2026). Simulations for Optimization of Proton Dose Delivery using the Advanced Markus Chamber. HNPS Advances in Nuclear Physics. ISSN 2654-007X. 32, p. 16–19. doi: 10.12681/hnpsanp.8679. Full text in Research Archive Show summary

  The Advanced Markus chamber is a vented, plane-parallel ionization chamber widely used in proton dosimetry, particularly in cases involving narrow spread-out Bragg peaks or steep depth-dose gradients. As part of the NuCapCure project, a series of in vitro and animal model irradiation experiments will be conducted to evaluate the efficacy of novel radiosensitive compounds designed to enhance the cancer cell-killing potential of proton therapy. To support these experiments, Monte Carlo simulations were carried out using the MCNP 6.1 code to model the irradiation setup at the Oslo Cyclotron Laboratory (OCL) that employs the MC-35 Scanditronix AB cyclotron. The computational model included the 16 MeV proton source, a tungsten filter, a beam monitor, and the Advanced Markus chamber. Special attention was paid to the effect of the chamber’s entrance window, as it influences the location of the proton Bragg peak. The results of this study allow the optimal positioning of both the Markus chamber and the biological samples, thereby maximizing dose delivery during proton irradiation experiments.

• Kalamara, A.; Stamatelatos, I.E.; Stefanopoulos, K.L.; Kalef-Ezra, J.A.; Georgakilas, A.G. & Stewart, R.D. [Show all 21 contributors for this article] (2025). A dosimetric and biological model for neutron capture therapy (NCT) experiments. Applied Radiation and Isotopes. ISSN 0969-8043. 226. doi: 10.1016/j.apradiso.2025.112233. Full text in Research Archive Show summary

  A hybrid Monte Carlo approach using MCNP in combination with the cell-level code Monte Carlo Damage Simulation (MCDS) is presented to support the design and analysis of experiments for the evaluation of gadolinium (Gd) based agents in neutron capture therapy (NCT). Monoenergetic neutrons (0.025 eV–15 MeV) and polyenergetic neutron beams from NEUTRA, ICON (PSI, Switzerland), and HK1 (LVR-15, Czech Republic) were used to estimate the relative biological effectiveness (RBE) of NCT for the biologically critical endpoint of DNA double strand break (DSB) production relative to 60Co γ-rays. Moreover, microdosimetric spectra of protons, electrons, alpha particles and heavy recoils were determined for the aforementioned neutron beams, to enhance the interpretation of energy deposition in subcellular structrures. The proposed, hybrid model and methodology builds on well-validated dosimetry and biophysical models at different spatial scales to create a versatile and generalized framework to estimate dosimetric parameters and RBE. This approach facilitates comparisons between NCT and low linear energy transfer (LET) radiation alternatives.

• Panagiotakis, Stylianos; Mavroidi, Barbara; Athanasopoulos, Alexandros; Gonçalves, Antonio Ricardo; Bugnicourt-Moreira, Loïc & Regagnon, Theo [Show all 15 contributors for this article] (2023). Small anticancer drug release by light: Photochemical internalization of porphyrin-β-cyclodextrin nanoparticles. Carbohydrate Polymers. ISSN 0144-8617. 306. doi: 10.1016/j.carbpol.2023.120579. Full text in Research Archive
• Ménard, Mathilde; Ali, Lamiaa M. A.; Vardanyan, Ani; Charnay, Clarence; Raehm, Laurence & Cunin, Frédérique [Show all 12 contributors for this article] (2023). Upscale Synthesis of Magnetic Mesoporous Silica Nanoparticles and Application to Metal Ion Separation: Nanosafety Evaluation. Nanomaterials. 13(24). doi: 10.3390/nano13243155. Full text in Research Archive
• Régagnon, Théo; Bugnicourt-Moreira, Loic; Ravaz, Romain; Idlas, Pierre; Ramousset, Lilly & Kouassi, Marie-Carole [Show all 11 contributors for this article] (2023). Photoresponsive liposomes and LipoParticles by incorporating a photosensitizer agent in their lipid membrane. Journal of Photochemistry and Photobiology A: Chemistry (JPPA). ISSN 1010-6030. 442. doi: 10.1016/j.jphotochem.2023.114765. Full text in Research Archive
• Grigalavicius, Mantas; Ezzatpanah, Somayeh; Papakyriakou, Athanasios; Henriksen-Raabe, Tine Therese; Yannakopoulou, Konstantina & Theodossiou, Theodossis (2022). 5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action. Cancers. 14(16). doi: 10.3390/cancers14164003. Full text in Research Archive
• Ali, Muhammad; Fulci, Giulia; Grigalavicius, Mantas; Pulli, Benjamin; Li, Anning & Wojtkiewicz, Gregory R. [Show all 11 contributors for this article] (2022). Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy. Neoplasia. ISSN 1522-8002. 26. doi: 10.1016/j.neo.2022.100779. Full text in Research Archive Show summary

  Background Host immune response is a critical component in tumorigenesis and immune escape. Radiation is widely used for glioblastoma (GBM) and can induce marked tissue inflammation and substantially alter host immune response. However, the role of myeloperoxidase (MPO), a key enzyme in inflammation and host immune response, in tumorigenesis after radiotherapy is unclear. In this study, we aimed to determine how post-radiation MPO activity influences GBM and outcome. Methods We injected C57BL/6J or MPO-knockout mice with 005 mouse GBM stem cells intracranially. To observe MPO's effects on post-radiation tumor progression, we then irradiated the head with 10 Gy unfractionated and treated the mice with a specific MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), or vehicle as control. We performed semi-quantitative longitudinal molecular MRI, enzymatic assays and flow cytometry to assess changes in inflammatory response and tumor size, and tracked survival. We also performed cell culture experiments in murine and human GBM cells to determine the effect of MPO on these cells. Results Brain irradiation increased the number of monocytes/macrophages and neutrophils, and boosted MPO activity by ten-fold in the glioma microenvironment. However, MPO inhibition dampened radiation-induced inflammation, demonstrating decreased MPO-specific signal on molecular MRI and attenuated neutrophil and inflammatory monocyte/macrophage recruitment to the glioma. Compared to saline-treated mice, both ABAH-treated and MPO-knockout mice had accelerated tumor growth and reduced survival. We further confirmed that MPO decreased tumor cell viability and proliferation in cell cultures. Conclusion Local radiation to the brain initiated an acute systemic inflammatory response with increased MPO-carrying cells both in the periphery and the GBM, resulting in increased MPO activity in the tumor microenvironment. Inhibition or absence of MPO activity increased tumor growth and decreased host survival, revealing that elevated MPO activity after radiation has an anti-tumor role.

• Christopoulos, Panagiotis; Grigalavicius, Mantas; Corthay, Alexandre; Berg, Kristian & Theodossiou, Theodossis (2021). Reactive Species from Two-Signal Activated Macrophages Interfere with Their Oxygen Consumption Measurements. Antioxidants. 10:1149(7), p. 1–12. doi: 10.3390/antiox10071149. Full text in Research Archive Show summary

  Metabolic modulation of macrophage activation has emerged as a promising strategy lately in immunotherapeutics. However, macrophages have a broad spectrum of functions and thus, understanding the exact metabolic changes that drive a particular immune response, is of major importance. In our previous work, we have reported a key role of nitric oxide (NO●) in two(2)-signal activated macrophages [M(2-signals)]. Further characterization using metabolic analysis in intact cells, showed that the basal and maximal respiration levels of M(2-signals) were comparable, with cells being unresponsive to the injections-inducd mitochondrial stress. Here, we show that excessive NO● secretion by the M(2-signals) macrophages, interferes with the oxygen (O2) consumption measurements on cells using the seahorse metabolic analyzer. This is attributed mainly to the consumption of ambient oxygen by NO● to form NO2− and/or NO3− but also to the reduction of O2 to superoxide anion (O2●−) by stray electrons from the electron transport chain, leading to the formation of peroxynitrite (ONOO−). We found that reactive species-donors in the absence of cells, produce comparable oxygen consumption rates (OCR) with M(2-signals) macrophages. Furthermore, inhibition of NO● production, partly recovered the respiration of activated macrophages, while external addition of NO● in non-activated macrophages downregulated their OCR levels. Our findings are crucial for the accurate metabolic characterization of cells, especially in cases where reactive nitrogen or oxygen species are produced in excess.

• Görgen, Andreas; Guttormsen, Magne Sveen; Larsen, Ann-Cecilie; Siem, Sunniva; Adli, Erik & Edin, Nina Frederike J [Show all 14 contributors for this article] (2021). The Oslo Cyclotron Laboratory. The European Physical Journal Plus. 136, p. 1–13. doi: 10.1140/epjp/s13360-021-01150-3. Full text in Research Archive Show summary

  Research at the Oslo Cyclotron Laboratory at the University of Oslo is focused on spectroscopy experiments for nuclear structure and nuclear astrophysics using the Oslo Scintillator Array OSCAR. Light-ion beams from the K=35 cyclotron are furthermore used for studies in radiation biology and medical physics, for research and development related to medical isotope production, and for irradiation of materials and electronics components. Here we present an overview of the laboratory and its research infrastructure, give a brief discussion of the respective research programs and methods, and present recent highlights.

• Li, Xue; Salzano, Giuseppina; Qiu, Jingwen; Ménard, Mathilde; Berg, Kristian & Theodossiou, Theodossis [Show all 8 contributors for this article] (2020). Drug-Loaded Lipid-Coated Hybrid Organic-Inorganic “Stealth” Nanoparticles for Cancer Therapy. Frontiers in Bioengineering and Biotechnology. doi: 10.3389/fbioe.2020.01027. Full text in Research Archive
• Jerjes, Waseem; Theodossiou, Theodossis; Hirschberg, Henry; Høgset, Anders; Weyergang, Anette & Selbo, Pål Kristian [Show all 9 contributors for this article] (2020). Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research. Journal of Clinical Medicine. 9(2). doi: 10.3390/jcm9020528. Full text in Research Archive Show summary

  Photochemical internalisation (PCI) is a unique intervention which involves the release of endocytosed macromolecules into the cytoplasmic matrix. PCI is based on the use of photosensitizers placed in endocytic vesicles that, following light activation, lead to rupture of the endocytic vesicles and the release of the macromolecules into the cytoplasmic matrix. This technology has been shown to improve the biological activity of a number of macromolecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus and oligonucleotides and certain chemotherapeutics, such as bleomycin. This new intervention has also been found appealing for intracellular delivery of drugs incorporated into nanocarriers and for cancer vaccination. PCI is currently being evaluated in clinical trials. Data from the first-in-human phase I clinical trial as well as an update on the development of the PCI technology towards clinical practice is presented here.

• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Arous, Delmon; Juzeniene, Asta; Ménard, Mathilde & Skarpen, Ellen [Show all 8 contributors for this article] (2020). Photodynamic efficacy of cercosporin in 3D tumor cell CCultures. Photochemistry and Photobiology. ISSN 0031-8655. 96(3), p. 699–707. doi: 10.1111/php.13257. Full text in Research Archive Show summary

  In the present work, we study the photodynamic action of cercosporin (cerco), a naturally occurring photosensitizer, on human cancer multicellular spheroids. U87 spheroids exhibit double the uptake of cerco than T47D and T98G spheroids as shown by flow cytometry on the single cell level. Moreover, cerco is efficiently internalized by cells throughout the spheroid as shown by confocal microscopy, for all three cell lines. Despite their higher cerco uptake, U87 spheroids show the least vulnerability to cerco‐PDT, in contrast to the other two cell lines (T47D and T98G). While 300 μm diameter spheroids consistently shrink and become necrotic after cerco PDT, bigger spheroids (>500 μm) start to regrow following blue‐light PDT and exhibit high viability. Cerco‐PDT was found to be effective on bigger spheroids reaching 1mm in diameter especially under longer exposure to yellow light (~590 nm). In terms of metabolism, T47D and T98G undergo a complete bioenergetic collapse (respiration and glycolysis) as a result of cerco‐PDT. U87 spheroids also experienced a respiratory collapse following cerco‐PDT, but retained half their glycolytic activity.

• Mastrangelopoulou, Maria; Grigalavicius, Mantas; Henriksen-Raabe, Tine Therese; Skarpen, Ellen; Juzenas, Petras & Qian, Peng [Show all 8 contributors for this article] (2020). Predictive biomarkers for 5-ALA-PDT can lead to personalized treatments and overcome tumor-specific resistances. Cancer Reports. p. 1–16. doi: 10.1002/cnr2.1278. Full text in Research Archive
• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Berg, Kristian; Arous, Delmon; Ménard, Mathilde & Henriksen-Raabe, Tine Therese [Show all 12 contributors for this article] (2019). Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production. Nature Communications. 10(1). doi: 10.1038/s41467-019-12042-7. Full text in Research Archive Show summary

  We demonstrate excitation of photosensitisers (PSs) by accelerated protons to produce fluorescence and singlet oxygen. Their fluorescence follows a pattern similar to the proton energy loss in matter, while proton-derived fluorescence spectra match the photon-induced spectra. PSs excited in dry gelatin exhibit enhanced phosphorescence, suggesting an efficient PSs triplet state population. Singlet oxygen measurements, both optically at ~1270 nm and through the photoproduct of protoporphyrin IX (PpIX), demonstrate cytotoxic singlet oxygen generation by proton excitation. The singlet oxygen-specific scavenger 1,4-diazabicyclo[2.2.2]octane (DABCO) abrogates the photoproduct formation under proton excitation, but cannot countermand the overall loss of PpIX fluorescence. Furthermore, in two cell lines, M059K and T98G, we observe differential cell death upon the addition of the PS cercosporin, while in U87 cells we see no effect at any proton irradiation dose. Our results pave the way for a novel treatment combining proton therapy and “proton-dynamic therapy” for more efficient tumour eradication.

• Mensali, Nadia; Dillard, Pierre; Hebeisen, Michael; Lorenz, Susanne; Theodossiou, Theodossis & Myhre, Marit Renee [Show all 12 contributors for this article] (2019). NK cells specifically TCR-dressed to kill cancer cells. EBioMedicine. 40, p. 106–117. doi: 10.1016/j.ebiom.2019.01.031. Full text in Research Archive Show summary

  Background Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs, T-cell receptors (TCRs) can recognize all cellular proteins, which expand NK-92 recognition to the whole proteome. Methods We herein genetically engineered NK-92 to express the CD3 signaling complex, and showed that it rendered them able to express a functional TCR. Functional assays and in vivo efficacy were used to validate these cells. Findings This is the first demonstration that a non-T cell can exploit TCRs. This TCR-redirected cell line, termed TCR-NK-92, mimicked primary T cells phenotypically, metabolically and functionally, but retained its NK cell effector functions. Our results demonstrate a unique manner to indefinitely produce TCR-redirected lymphocytes at lower cost and with similar therapeutic efficacy as redirected T cells. Interpretation These results suggest that an NK cell line could be the basis for an off-the-shelf TCR-based cancer immunotherapy solution.

• Theodossiou, Theodossis; Ali, Muhammad; Grigalavicius, Mantas; Grallert, Beata; Dillard, Pierre & Schink, Kay Oliver [Show all 12 contributors for this article] (2019). Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT-tamoxifen hybrid therapy. NPJ breast cancer. doi: 10.1038/s41523-019-0108-8. Full text in Research Archive
• Våtsveen, Thea Kristin; Myhre, Marit Renee; Steen, Chloe Beate; Wälchli, Sébastien; Lingjærde, Ole Christian & Bai, Baoyan [Show all 14 contributors for this article] (2018). Artesunate shows potent anti-tumor activity in B-cell lymphoma. Journal of Hematology & Oncology. 11:23, p. 1–12. doi: 10.1186/s13045-018-0561-0. Full text in Research Archive Show summary

  Background Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate has previously been identified as a growth suppressor in some cancer types and was tested as a new treatment option in B-cell lymphoma. Methods We included artesunate in a cancer sensitivity drug screen in B lymphoma cell lines. The preclinical properties of artesunate was tested as single agent in vitro in 18 B-cell lymphoma cell lines representing different histologies and in vivo in an aggressive B-cell lymphoma xenograft model, using NSG mice. Artesunate-treated B lymphoma cell lines were analyzed by functional assays, gene expression profiling, and protein expression to identify the mechanism of action. Results Drug screening identified artesunate as a highly potent anti-lymphoma drug.Artesunate induced potent growth suppression in most B lymphoma cells with an IC50 comparable to concentrations measured in serum from artesunate-treated malaria patients, while leaving normal B-cells unaffected. Artesunate markedly inhibited highly aggressive tumor growth in a xenograft model. Gene expression analysis identified endoplasmic reticulum (ER) stress and the unfolded protein response as the most affected pathways and artesunate-induced expression of the ER stress markers ATF-4 and DDIT3 was specifically upregulated in malignant B-cells, but not in normal B-cells. In addition, artesunate significantly suppressed the overall cell metabolism, affecting both respiration and glycolysis. Conclusions Artesunate demonstrated potent apoptosis-inducing effects across a broad range of B-cell lymphoma cell lines in vitro, and a prominent anti-lymphoma activity in vivo, suggesting it to be a relevant drug for treatment of B-cell lymphoma.

• Mastrangelopoulou, Maria; Grigalavicius, Mantas; Berg, Kristian; Ménard, Mathilde & Theodossiou, Theodossis (2018). Cytotoxic and Photocytotoxic Effects of Cercosporin on Human Tumor Cell Lines. Photochemistry and Photobiology. ISSN 0031-8655. p. 1–10. doi: 10.1111/php.12997. Full text in Research Archive
• Sideratou, Zili; Agathokleous, Maria; Theodossiou, Theodossis & Tsiourvas, Dimitris (2018). Functionalized Hyperbranched Polyethylenimines as Thermosensitive Drug Delivery Nanocarriers with Controlled Transition Temperatures. Biomacromolecules. ISSN 1525-7797. 19(2), p. 315–328. doi: 10.1021/acs.biomac.7b01325. Full text in Research Archive
• Katheder, Nadja Sandra; Khezri, Rojyar; O'Farrell, Fergal; Schultz, Sebastian; Jain, Ashish & Rahman, Mohammed Mahidur [Show all 14 contributors for this article] (2017). Microenvironmental autophagy promotes tumour growth. Nature. ISSN 0028-0836. 541(7637), p. 417–420. doi: 10.1038/nature20815. Full text in Research Archive
• Theodossiou, Theodossis; Olsen, Cathrine Elisabeth; Jonsson, Marte; Kubin, Andreas; Hothersall, John S. & Berg, Kristian (2017). The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy. Redox Biology. 12, p. 191–197. doi: 10.1016/j.redox.2017.02.018. Full text in Research Archive
• Olsen, Cathrine Elisabeth; Sellevold, Simen; Theodossiou, Theodossis; Patzke, Sebastian & Berg, Kristian (2017). Impact of genotypic and phenotypic differences in sarcoma models on the outcome of photochemical internalization (PCI) of bleomycin. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 20, p. 35–47. doi: 10.1016/j.pdpdt.2017.08.010. Full text in Research Archive
• Theodossiou, Theodossis; Waelchli, Sebastien; Olsen, Cathrine Elisabeth; Skarpen, Ellen & Berg, Kristian (2016). Deciphering the nongenomic, mitochondrial toxicity of tamoxifens as determined by cell metabolism and redox activity. ACS Chemical Biology. ISSN 1554-8929. 11(1), p. 251–262. doi: 10.1021/acschembio.5b00734. Full text in Research Archive
• Pefkianakis, Eleftherios K; Theodossiou, Theodossis; Toubanaki, Dimitra K; Karagouni, Evdokia; Falaras, Polycarpos & Papadopoulos, Kyriakos [Show all 7 contributors for this article] (2015). A Family of Potent Ru(II) Photosensitizers with Enhanced DNA Intercalation: Bimodal Photokillers. Photochemistry and Photobiology. ISSN 0031-8655. 91(5), p. 1191–1202. doi: 10.1111/php.12485. Full text in Research Archive
• Theodossiou, Theodossis; Gonçalves, Antonio Ricardo; Yannakopoulou, Konstantina; Skarpen, Ellen & Berg, Kristian (2015). Photochemical internalization of tamoxifens transported by a "trojan-horse" nanoconjugate into breast-cancer cell lines. Angewandte Chemie International Edition. ISSN 1433-7851. 54(16), p. 4885–4889. doi: 10.1002/anie.201500183. Full text in Research Archive
• Aggelidou, Chrysie; Theodossiou, Theodossis; Gonçalves, Antonio Ricardo; Lampropoulou, Mariza & Yannakopoulou, Konstantina (2014). A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry. Beilstein Journal of Organic Chemistry. ISSN 2195-951X. 10, p. 2414–2420. doi: 10.3762/bjoc.10.251. Full text in Research Archive

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• Theodossiou, Theodossis & Meir, Michaela Georgine (2026). Pioneering study on a small molecule called phenazine methosulfate (PMS). doi: https:/www.linkedin.com/feed/update/urn:li:activity:7472287357455650817. Full text in Research Archive Show summary

  Members of our Norwegian Nuclear Research Centre community have co‑authored a pioneering study on a small molecule called phenazine methosulfate (PMS). The work conducted on brain cancer cells shows that PMS can briefly “jump‑start” energy production, even when the respirational energy systems are blocked by drugs ...

• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Berg, K.; Arous, Delmon; Ménard, M. & Raabe-Henriksen, T. [Show all 12 contributors for this article] (2021). Publisher Correction: Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production (Nature Communications, (2019), 10, 1, (3986), 10.1038/s41467-019-12042-7). Nature Communications. 12(1). doi: 10.1038/s41467-021-27175-x. Full text in Research Archive
• Christensen, Terje; Gruijl, Frank De; Hamblin, Michael; Ishibashi, Yukihide; Kamada, Kenji & Sage, Evelyne [Show all 10 contributors for this article] (2018). Outstanding Reviewers for: Photochemical and Photobiological Sciences in 2017. Photochemical and Photobiological Sciences. ISSN 1474-905X. 17(5), p. 533–533. doi: 10.1039/c8pp90021c. Full text in Research Archive

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