Theodossis Athanassios Theodossiou

Theodossis Athanassios Theodossiou
Oslo University Hospital · Institute for Cancer Research

Ph.D

About

87
Publications
21,413
Reads
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2,025
Citations
Citations since 2017
26 Research Items
1168 Citations
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2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Introduction
Theodossis Athanassios Theodossiou currently works at the Institute for Cancer Research, Oslo University Hospital as a project group leader. Theodossis does research in Medical Physics, Biophysics Biochemistry, Radiobiology and Cancer Research. Some of his current niches are PDT, bio/chemi-luminescent PDT, protonics, second harmonic generation from tissue, mitochondrial medicine, cell metabolism and drug delivery/nanotechnology.
Additional affiliations
January 2018 - April 2019
Oslo University Hospital
Position
  • Group Leader
October 2015 - December 2017
Oslo University Hospital
Position
  • Senior Researcher
June 2013 - October 2015
Oslo University Hospital
Position
  • Senior Researcher

Publications

Publications (87)
Article
Full-text available
The absorbed dose in vials containing photo-sensitizer solutions irradiated under neutron beams produced by the p-Li, D-D and D-T reactions was calculated. Monte Carlo simulations were performed by coupling the NeuSDesc and MCNP codes in order to derive the neutron energy spectrum, fluence and absorbed dose with depth in the samples. The absorbed d...
Article
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In a course of metabolic experiments, we determined that the addition of δ-aminolevulinic acid (5 ALA) to a panel of glioblastoma multiforme (GBM) cells caused a steep reduction in their glycolytic activity. This reduction was accompanied by a decrease in adenosine triphosphate (ATP) production from glycolysis. These results suggested that 5 ALA is...
Article
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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...
Article
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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...
Article
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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 $$K=35$$ K = 35 cyclotron are furthermore used for studies in radiation biology and medical physics, for research and development...
Article
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Hybrid porous nanoscale metal organic frameworks (nanoMOFs) made of iron trimesate are attracting increasing interest as drug carriers, due to their high drug loading capacity, biodegradability, and biocompatibility. NanoMOF surface modification to prevent clearance by the innate immune system remains still challenging in reason of their high poros...
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Background Photodynamic therapy (PDT) is a minimally invasive, clinically approved therapy with numerous advantages over other mainstream cancer therapies. 5‐aminolevulinic acid (5‐ALA)‐PDT is of particular interest, as it uses the photosensitiser PpIX, naturally produced in the heme pathway, following 5‐ALA administration. Even though 5‐ALA‐PDT sh...
Article
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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 throughou...
Article
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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 cytopla...
Article
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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 a...
Article
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Currently the greatest challenge in oncology is the lack of homogeneity of the lesions where different cell components respond differently to treatment. There is growing consensus that monotherapies are insufficient to eradicate the disease and there is an unmet need for more potent combinatorial treatments. We have previously shown that hypericin...
Article
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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 Nat...
Article
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Cercosporin is a naturally occurring perylenequinone. Although other perylenequinones have been extensively studied as photosensitizers in photodynamic therapy of cancer (PDT), cercosporin has been studied in this light only within the remits of phytopathology. Herein we investigated the photocytotoxicity of cercosporin against two glioblastoma mul...
Article
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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 inclu...
Article
The low critical solution temperature phase transition (Tc) that is exhibited by thermosensitive polymers is strongly dependent on polymer concentration, pH, ionic strength, as well as on the presence of specific molecules or ions in solution. Therefore, polymers with Tc values above 37 oC that are useful for hyperthermia therapy are not readily av...
Article
The low curative response to current treatment regimens for most soft tissue sarcomas indicates a strong need for alternative treatment strategies and predictive markers for treatment outcome. PCI (photochemical internalization) is a novel treatment strategy to translocate drugs into cytosol that otherwise would have been degraded in lysosomes. Two...
Article
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The diverse responses of different cancers to treatments such as photodynamic therapy of cancer (PDT) have fueled a growing need for reliable predictive markers for treatment outcome. In the present work we have studied the differential response of two phenotypically and genotypically different breast adenocarcinoma cell lines, MCF7 and MDA-MB-231,...
Article
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As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster ma...
Article
Tamoxifen is not only considered a very potent chemotherapeutic adjuvant for estrogen receptor positive breast cancers, but also a very good chemo-preventive drug. Recently there has been a rising amount of evidence for a non-genomic cytotoxicity of tamoxifen, even in estrogen receptor negative cells, which has greatly confounded researchers. Clini...
Article
A new family of Ru(II)-based photosensitizers was synthesized and systematically characterized. The ligands employed to coordinate the ruthenium metal center were the commercially-available 2,2'-bipyridine and a pyridine-quinoline hybrid bearing an anthracene moiety. The complexes obtained carry either PF6 (-) or Cl(-) counterions. These counterion...
Article
Photochemical internalization (PCI) has shown great promise as a therapeutic alternative for targeted drug delivery by light-harnessed activation. However, it has only been applicable to therapeutic macromolecules or medium-sized molecules. Herein we describe the use of an amphiphilic, water-soluble porphyrin–β-cyclodextrin conjugate (mTHPP-βCD) as...
Article
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Grafting of δ-aminolevulinic acid (1) moieties on the narrow periphery of a β-cyclodextrin (β-CD) derivative through hydrolysable bonds was implemented, in order to generate a water-soluble, molecular/drug carrier with the capacity to undergo intracellular transformation into protoporphyrin IX (PpIX), an endogenous powerful photosensitizer for phot...
Article
Hydroxyethyl Starch (HES) was interacted with succinic anhydride affording a carboxylated derivative which has proved to be a promising polymeric drug delivery system. Specifically, this polymer is conveniently prepared, is biodegradable, non-immunogenic, and can encapsulate doxorubicin due to the protonation of the primary amino group of doxorubic...
Article
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Apolipoprotein (apo) E4 isoform has consistently emerged as a susceptibility factor for late-onset Alzheimers disease (AD) although the exact mechanism is not clear. A rare apoE4 mutant, apoE4[L28P] Pittsburgh, burdens carriers with added risk for late-onset AD and may be a useful tool for gaining insight on the role of apoE4 in disease pathogenesi...
Article
We report the design, preparation, and properties of a nanoaggregate formed in phosphate buffer solution by a porphyrin-β-cyclodextrin (β-CD) conjugate and a nitric oxide photodonor tailored to fit the β-CD cavity. The small nanoassembly with a diameter of about 13 nm exhibits the typical red fluorescence of the porphyrin chromophore. The empty cav...
Article
I can't get NO satisfaction: 6-Mono- and 6-multi-S-nitroso-β-cyclodextrins (SNO-βCDs) were characterized in terms of their SNO content, conformational preference, thermal and photochemical release of NO, and their ability to encapsulate guest molecules, as well as cell permeation and toxicity. SNO-βCDs are promising bimodal molecules of satisfactor...
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To develop a novel hyperbranched polymer-based nanocarrier for efficient drug delivery to cell mitochondria. Also to study for the first time the cytotoxic effect of doxorubicin via mitochondria-specific delivery system. We introduced alkyltriphenylphosphonium groups (TPP) to a poly(ethylene imine) hyperbranched polymer (PEI). We harnessed the hydr...
Article
Topical or systemic administration of 5-aminolevulinic acid (ALA) and its esters results in increased production and accumulation of protoporphyrin IX (PpIX) in cancerous lesions allowing effective application of Photodynamic Therapy (PDT). The large concentrations of exogenous ALA practically required to bypass the negative feedback control exerte...
Article
Recently, a nongenomic cytotoxic component of the chemotherapeutic agent tamoxifen (TAM) has been identified that predominantly triggers mitochondrial events. The present study delineates the intracellular fate of TAM and studies its interaction with a spectrum of cell homeostasis modulators primarily relevant to mitochondria. The subcellular local...
Article
New and emerging therapeutic approaches focus on the targeted delivery of therapeutic agents to cell mitochondria with high specificity. Herein we present a novel mitotropic nanocarrier based on an oligolysine scaffold by addition of two triphenylphosphonium cations per oligomer. Although the parent oligolysine failed to enter healthy cells, the tr...
Article
Based on a commercially available hyperbranched aliphatic polyester, novel multifunctional gadolinium complexes were prepared bearing protective PEG chains, a folate targeting ligand and EDTA or DTPA chelate moieties. Their relatively high water relaxivity values coupled with biodegradability of the hyperbranched scaffold, folate receptor specifici...
Article
Hypericin hydroquinone is the product of two-electron reduction of hypericin (quinone), a potent phenanthroperylenequinone photosensitizer. In contrast to the quinone, the hydroquinone exhibits strong absorbance in the far-red spectral region. Herein we provide initial evidence on the potential of hypericin hydroquinone as a far-red photosensitizer...
Article
Photodynamic therapy (PDT) is an established anticancer treatment employing a phototoxin (photosensitizer), visible light and oxygen. The latter is photochemically converted into reactive oxygen species, which are highly toxic to the cells. Hypericin, a natural pigment of hypericum plants, is prominent among photosensitizers. The unique perylenequi...
Article
In the present review the crucial role of the guanidinium functional group in facilitating the transport of dendritic polymers through liposomal and cell membranes is discussed, along with other structural features of guanidinylated dendritic polymers that fine-tune their transport properties, and even determine their subcellular destinations. In t...
Article
We have developed novel cocktail liposomes bearing doxorubicin in their hydrophilic cores, and amiodarone, a potent multidrug resistance inhibitor, in their lipid bilayers. The efficacy of these liposomes was studied in DU145 human prostate carcinoma cells. Intracellular calcein retention, which is inversely proportional to multidrug resistance act...
Article
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The effect of hypericin photoactivation on mitochondria of human prostate carcinoma cells was studied using a range of mitochondrial inhibitors. Oligomycin significantly enhanced hypericin phototoxicity while atractyloside and antymicin A conferred a significant protection. Use of myxothiazol did not affect cell survival following hypericin photoac...
Article
A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aq...
Article
Hypericin (HYP), a photocytotoxic phenanthroperylenquinone was encapsulated in liposomes outfitted with guanidinium-bearing lipids to ensure efficient cell binding through molecular recognition with anionic groups resident on the plasma membrane. The uptake of HYP encapsulated in these liposomes by DU145 human prostate cancer cells, was studied emp...
Article
Two generations of poly(l-lysine) dendrigrafts (DGLs) were studied with regard to their ability to interact with and translocate through liposomal and cellular membranes. Partial guanidinylation of the surface amino groups of the starting dendrigrafts afforded the guanidinylated derivatives whose membrane translocation properties were also assessed...
Article
The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the...
Article
We performed second harmonic generation (SHG) imaging of collagen in rat-tendon cryosections, using femtosecond laser scanning confocal microscopy, both in backscattering and transmission geometries. SHG transmission images of collagen fibers were spatially resolved due to a coherent, directional SHG component. This effect was enhanced with the use...
Article
Hypericin, a naturally occurring anthraquinone synthesised by hypericum, upon light activation exhibits photodynamic cytotoxicity attributed mainly to the production of reactive oxygen species. This study aimed to elucidate the primary subcellular targets and mechanistic aspects of hypericin photosensitization in human prostate carcinoma cells. Dep...
Article
We have assessed photoinduced toxicity of hypericin in PAM 212 murine keratinocytes and the relationship between concentration, incubation time and light fluence to evaluate the effect of intracellular aggregation at high concentrations. Confocal microscopy was used to establish the subcellular localization of hypericin at 5 and 50 microM and incub...
Article
Full-text available
Photodynamic therapy (PDT) of cancer (1, 2) is a well-established treatment modality that uses light excitation of a photosensitive substance to produce oxygen-related cytotoxic intermediates, such as singlet oxygen or free radicals (3, 4). Although PDT is advantageous over other forms of cancer treatments because of its limited side effects, its m...
Article
Full-text available
There is concern that the delicate fibres and cylindrical diffuser tips used for intraluminal PDT of blood vessels might break during the treatment. We have developed and tested a simple system to monitor for fibre breakage during PDT. Light from the laser is passed through a beam expander, then a beam splitter, and then is again contracted into th...
Article
A comparative study of the cellular photosensitizing properties of protoporphyrin IX (PpIX) and photoprotoporphyrin (Ppp) was carried out in the transformed murine keratinocyte cell line, PAM 212. Time-course fluorescence studies were performed to determine the rate of uptake by cells together with fluorescence microscopy. The sensitized cells were...
Article
A comparative study of the cellular photosensitizing properties of protoporphyrin IX (PpIX) and photoprotoporphyrin (Ppp) was carried out in the transformed murine keratinocyte cell line, PAM 212. Time‐course fluorescence studies were performed to determine the rate of uptake by cells together with fluorescence microscopy. The sensitized cells were...
Article
Full-text available
Irreversible thermal conformational changes induced to collagen have been studied by optical methods. More specifically, second harmonic generation (SHG) from incident nanosecond Ng:YAG 1064 nm radiation and laser-induced fluorescence by 337 nm, pulsed nanosecond nitrogen laser excitation, at 405, 410 and 415 nm emission wavelengths were registered...
Article
Full-text available
Irreversible thermal conformational changes induced to collagen have been studied by optical methods. More specifically, second harmonic generation (SHG) from incident nanosecond Ng:YAG 1064 nm radiation and laser-induced fluorescence by 337 nm, pulsed nanosecond nitrogen laser excitation, at 405, 410 and 415 nm emission wavelengths were registered...
Article
Full-text available
The B 2(Sigma) +->X2(Sigma) + violet band emission spectrum of CN following laser ablation of type I collagen was exploited for the estimation of the transient temperature of the plasma plume and consequently of the sample surface considering thermodynamic equilibrium. The temperature dependence upon experimental parameters, such as laser intensity...
Article
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A novel detection method for malignant tumour detection through specific accumulation of far-red emitting photosensitisers, has been developed. The set-up, based on He-Ne (633 nm) excitation was tested with phantom malignancies models using photosensitisers on chicken tissue. Intensity vs. depth of tissue measurements as well as photobleaching meas...
Article
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In the course of work aimed to examine second harmonic generation in biological macromolecules, it was discovered that 1064 nm pulsed nanosecond infrared laser radiation, after scattering on the optically rough sample surface, was perceived as double the fundamental frequency green speckle pattern by the unaided eye. The threshold of this arresting...
Article
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Emission and excitation spectra of collagen were recorded in the ultraviolet and visible regions. The existence of several types of chromophores absorbing and emitting throughout these spectral regions was observed. It was shown that laser irradiation at 355 and 532 nm caused collagen fluorescence photobleaching by 30%, when the delivered light dos...
Article
Full-text available
Under high-intensity nanosecond 1064 nm irradiation of a collagen-rhodamine 6G (R6G) system, multiquantum excitation of the R6G molecules to their S2 state was facilitated. The observation of this effect was achieved through associated energy transfer to the resonant collagen excited state band. Analogous cascaded energy transfer phenomena, resulti...