Odrun Arna Gederaas

• Swaminathan, Priyanka; Klingstedt, Therése; Theologidis, Vasileios; Gram, Hjalte; Larsson, Johan & Hagen, Lars [Show all 12 contributors for this article] (2024). In Vitro Cell Model Investigation of Alpha-Synuclein Aggregate Morphology Using Spectroscopic Imaging. International Journal of Molecular Sciences. ISSN 1661-6596. 25(22). doi: 10.3390/ijms252212458. Full text in Research Archive Show summary

  Recently, it has been hypothesized that alpha-synuclein protein strain morphology may be associated with clinical subtypes of alpha-synucleinopathies, like Parkinson’s disease and multiple system atrophy. However, direct evidence is lacking due to the caveat of conformation-specific characterization of protein strain morphology. Here we present a new cell model based in vitro method to explore various alpha-synuclein (αsyn) aggregate morphotypes. We performed a spectroscopic investigation of the HEK293 cell model, transfected with human wildtype-αsyn and A53T-αsyn variants, using the amyloid fibril-specific heptameric luminescent oligomeric thiophene h-FTAA. The spectral profile of h-FTAA binding to aggregates displayed a blue-shifted spectrum with a fluorescence decay time longer than in PBS, suggesting a hydrophobic binding site. In vitro spectroscopic binding characterization of h-FTAA with αsyn pre-formed fibrils suggested a binding dissociation constant Kd < 100 nM. The cells expressing the A53T-αsyn and human wildtype-αsyn were exposed to recombinant pre-formed fibrils of human αsyn. The ensuing intracellular aggregates were stained with h-FTAA followed by an evaluation of the spectral features and fluorescence lifetime of intracellular αsyn/h-FTAA, in order to characterize aggregate morphotypes. This study exemplifies the use of cell culture together with conformation-specific ligands to characterize strain morphology by investigating the spectral profiles and fluorescence lifetime of h-FTAA, based upon its binding to a certain αsyn aggregate. This study paves the way for toxicity studies of different αsyn strains in vitro and in vivo. Accurate differentiation of specific alpha-synucleinopathies is still limited to advanced disease stages. However, early subtype-specific diagnosis is of the utmost importance for prognosis and treatment response. The potential association of αsyn aggregates morphotypes detected in biopsies or fluids to disease phenotypes would allow for subtype-specific diagnosis in subclinical disease stage and potentially reveal new subtype-specific treatment targets. Notably, the method may be applied to the entire spectrum of neurodegenerative diseases by using a combination of conformation-specific ligands in a physicochemical environment together with other types of polymorphic amyloid variants and assess the conformation-specific features of various protein pathologies.

• Gederaas, Odrun Arna; Lindgren, Mikael; Stigen, Kari; Høgset, Anders Skog & Hirschberg, Henry (2024). Pharmacokinetics of disulphonated tetraphenyl chlorin (fimaporfin/TPCS<inf>2a</inf>) in a rat glioma model - methodology. Journal of Porphyrins and Phthalocyanines. ISSN 1088-4246. 28(5), p. 291–299. doi: 10.1142/S1088424624500238. Full text in Research Archive
• Gederaas, Odrun Arna; Sharma, Animesh; Mbarak, Saide; Sporsheim, Bjørnar; Høgset, Anders & Bogoeva, Vanya [Show all 8 contributors for this article] (2023). Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells. Molecular Omics. 19(7), p. 585–597. doi: 10.1039/d2mo00337f. Full text in Research Archive Show summary

  Photochemical internalization (PCI) is a promising new technology for site-specific drug delivery, developed from photodynamic therapy (PDT). In PCI, light-induced activation of a photosensitizer trapped inside endosomes together with e.g. chemotherapeutics, nucleic acids or immunotoxins, allows cytosolic delivery and enhanced local therapeutic effect. Here we have evaluated the photosensitizer meso-tetraphenyl chlorine disulphonate (TPCS2a/fimaporfin) in a proteome analysis of AY-27 rat bladder cancer cells in combination with the chemotherapeutic drug bleomycin (BML). We find that BLMPCI attenuates oxidative stress responses induced by BLM alone, while concomitantly increasing transcriptional repression and DNA damage responses. BLMPCI also mediates downregulation of bleomycin hydrolase (Blmh), which is responsible for cellular degradation of BLM, as well as several factors known to be involved in fibrotic responses. PCI-mediated delivery might thus allow reduced dosage of BLM and alleviate unwanted side effects from treatment, including pulmonary fibrosis.

• Hageberg, Ingvild Uri; Arja, Katriann; Vindstad, Benedikte Emilie; Bergvoll, Johannes; Gederaas, Odrun Arna & Melø, Thor Bernt [Show all 8 contributors for this article] (2023). Photophysics of Glycosylated Ring-Fused Chlorin Complexes and Their Photosensitizing Effects on Cancer Cells. ChemPhotoChem. 7(8). doi: 10.1002/cptc.202300028. Full text in Research Archive Show summary

  The future of photodynamic therapy (PDT) as a promising cancer treatment relies on the development of new selective and effective photosensitizers (PS) with improved photophysical and biochemical qualities. Herein, we present the synthetic procedure, photophysical properties and photosensitizing effects of novel glycosylated 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine] fused chlorin agents featuring either glucose, galactose, or N-acetyl glucosamine. It is shown that both the proto- and Zn2+-ion forms of the ring-stabilized glycochlorins exhibit the required photophysical properties in terms of triplet excited states and singlet oxygen generation, the latter more than 50 % in organic solvents such as CHCl3. Employing the rat AY-27 and human T24 cancer cell models, it was found that these are superior to the corresponding unglycosylated chlorin in biological activity, and moreover, the proto form is 2–3 times superior to the Zn-stabilized variant. Provisional flow cytometry and cell localization studies of the proto-form indicate both necrotic and apoptotic biological activity, and that the photosensitizer localizes in the mitochondria, cell membrane and lysosomes. However, the localization into the lysosomes is dominating and increases substantially with time. We anticipate the findings will aid in the development of photosensitizers for targeted cancer PDT.

• Desgranges, Stéphane; Juzenas, Petras; Vasovic, Vlada; Gederaas, Odrun Arna; Lindgren, Mikael & Warloe, Trond [Show all 8 contributors for this article] (2022). Amphiphilic Protoporphyrin IX Derivatives as New Photosensitizing Agents for the Improvement of Photodynamic Therapy. Biomedicines. 10(2). doi: 10.3390/biomedicines10020423. Full text in Research Archive Show summary

  Photodynamic therapy (PDT) is a non-invasive therapeutic modality based on the interaction between a photosensitive molecule called photosensitizer (PS) and visible light irradiation in the presence of oxygen molecule. Protoporphyrin IX (PpIX), an efficient and widely used PS, is hampered in clinical PDT by its poor water-solubility and tendency to self-aggregate. These features are strongly related to the PS hydrophilic–lipophilic balance. In order to improve the chemical properties of PpIX, a series of amphiphilic PpIX derivatives endowed with PEG550 headgroups and hydrogenated or fluorinated tails was synthetized. Hydrophilic–lipophilic balance (HLB) and log p-values were computed for all of the prepared compounds. Their photochemical properties (spectroscopic characterization, photobleaching, and singlet oxygen quantum yield) were also evaluated followed by the in vitro studies of their cellular uptake, subcellular localization, and photocytotoxicity on three tumor cell lines (4T1, scc-U8, and WiDr cell lines). The results confirm the therapeutic potency of these new PpIX derivatives. Indeed, while all of the derivatives were perfectly water soluble, some of them exhibited an improved photodynamic effect compared to the parent PpIX.

• Gederaas, Odrun Arna; Sørensen, Andreas; Lindgren, Mikael; Melø, Thor Bernt; Altin, Dag & Flatby, Ellen M. Samdahl [Show all 8 contributors for this article] (2022). Synthesis and in vitro evaluation of a novel thienopyrimidine with phototoxicity towards rat glioma F98 cells. Journal of Photochemistry and Photobiology. ISSN 2666-4690. 10. doi: 10.1016/j.jpap.2022.100114. Full text in Research Archive Show summary

  Glioblastoma multiforme is one of the most aggressive cancer forms in humans, and has low recovery rates after surgery, ionizing radiation and chemotherapy. Therefore, there is a high interest in the development of new treatment methods, as for instance photodynamic therapy (PDT). It is here presented results of the cytotoxic properties of the novel compound N1-(4-(4-(benzyl(methyl)amino)thieno[2,3-d]pyrimidin-6-yl)benzyl)-N2,N2-dimethylethane-1,2-diamine (1), which was found ten-fold more active on the rat glioma cell model F98 than the reference drug Temozolomide (TMZ). Further cell survival studies showed a profound increase in F98 cell death on UVA-radiation (330 nm, 0.5 mW/cm2). Photochemical internalization induced delivery of compound 1, but in contrast to the cytostatic drug Bleomycin, a higher cytotoxicity was not observed. Localization studies using fluorescence microscopy revealed that compound 1 readily internalized into the cytosol but did not enter the cell nucleus. The compound was shown to be a relatively weak epidermal growth factor receptor inhibitor, which is not likely to explain its cytotoxicity. However, the quantum efficiency for generation of singlet oxygen was 23%, suggesting generation of reactive oxygen species as one possible mechanism. Although more studies are needed to reveal detailed mode of action, compound 1 is a promising photosensitizer candidate for further development in tests of animal models.

• Shi, L.; Pohla, H.; Buchner, A.; Zhang, L.; Pongratz, T. & Ruhm, A. [Show all 11 contributors for this article] (2020). MOP-dependent enhancement of methadone on the effectiveness of ALA-PDT for A172 cells by upregulating phosphorylated JNK and BCL2. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 30, p. 101657–101657. doi: 10.1016/j.pdpdt.2020.101657. Full text in Research Archive
• Nguyen, Jimmi; J, Steen Madsen; Gederaas, Odrun Arna; Berg, Kristian; Høgset, Anders & Hirschberg, Henry (2020). Ultrasonic Activation of the Sonosensitizer Fimaporfin Enhances the Efficacy of Chemotherapy: An In Vitro Study on Rat Glioma Cells. Journal of Cancer Research and Clinical Oncology. ISSN 0171-5216. doi: 10.31487/j.COR.2020.05.10. Full text in Research Archive
• Einrem, Rune F.; Alemayehu, Abraham; Borisov, Sergey M.; Ghosh, Abhik & Gederaas, Odrun Arna (2020). Amphiphilic rhenium-oxo corroles as a new class of sensitizers for photodynamic therapy. ACS Omega. 5(18), p. 10596–10601. doi: 10.1021/acsomega.0c01090. Full text in Research Archive Show summary

  A set of rhenium(V)-oxo <i>meso</i>-triarylcorroles bearing ester and carboxylic acid functionalities were synthesized with a view to determining their potential for photodynamic therapy. Toward this end, we measured their near-IR phosphorescence and their ability to sensitize singlet oxygen formation. The two esters studied, Re^VO 5,10,15-tris(<i>meta</i>-carbomethoxyphenyl)corrole and Re^VO 5,10,15-tris(<i>para</i>-carbomethoxyphenyl)corrole, were found to exhibit phosphorescence quantum yields of around 1% and fairly long phosphorescence lifetimes of about 60 μs in toluene. The corresponding carboxylic acids, which were examined in ethanolic/aqueous media, in contrast, showed much lower phosphorescence quantum yields on the order of 0.01% and somewhat shorter phosphorescent lifetimes. The quantum yields for singlet oxygen formation, on the other hand, turned out to be equally high (0.72 ± 0.02) for the esters and corresponding carboxylic acids. For the two carboxylic acids, we also carried out photocytotoxicity measurements on rat bladder cancer cells (AY27) and human colon carcinoma cells (WiDr). Cell viability measurements (MTT assays) indicated 50% cell death (LD₅₀) for AY27 cells upon 5 min of blue light exposure with the meta carboxylic acid and upon 7 min of exposure with the para carboxylic acid; complete cell death resulted after 20 min for both compounds. The WiDr cells proved less sensitive, and LD₅₀ values were reached after 8 and 12 min illumination with the meta and para carboxylic acids, respectively.

• Lindgren, Mikael; Gederaas, Odrun Arna; Siksjø, Monica; Hansen, Tom Andre; Chen, Lena & Mettra, Bastien [Show all 8 contributors for this article] (2020). Influence of Polymer Charge on the Localization and Dark- and Photo-Induced Toxicity of a Potential Type I Photosensitizer in Cancer Cell Models. Molecules. ISSN 1431-5157. 25(5). doi: 10.3390/molecules25051127. Full text in Research Archive Show summary

  A current trend within photo-dynamic therapy (PDT) is the development of molecular systems targeting hypoxic tumors. Thus, type I PDT sensitizers could here overcome traditional type II molecular systems that rely on the photo-initiated production of toxic singlet oxygen. Here, we investigate the cell localization properties and toxicity of two polymeric anthracene-based fluorescent probes (neutral Ant-PHEA and cationic Ant-PIm). The cell death and DNA damage of Chinese hamster ovary cancer cells (CHO-K1) were characterized as combining PDT, cell survival studies (MTT-assay), and comet assay. Confocal microscopy was utilized on samples incubated together with either DRAQ5, Lyso Tracker Red, or Mito Tracker Deep Red in order to map the localization of the sensitizer into the nucleus and other cell compartments. While Ant-PHEA did not cause significant damage to the cell, Ant-PIm showed increased cell death upon illumination, at the cost of a significant dark toxicity. Both anthracene chromophores localized in cell compartments of the cytosol. Ant-PIm showed a markedly improved selectivity toward lysosomes and mitochondria, two important biological compartments for the cell’s survival. None of the two anthracene chromophores showed singlet oxygen formation upon excitation in solvents such as deuterium oxide or methanol. Conclusively, the significant photo-induced cell death that could be observed with Ant-PIm suggests a possible type I PDT mechanism rather than the usual type II mechanism.

• Callaghan, Susan; Vindstad, Benedikte Emilie; Flanagan, Keith J.; Melø, Thor Bernt; Lindgren, Mikael & Grendstad, Kristin [Show all 8 contributors for this article] (2020). Structural, photophysical, and photobiological studies on BODIPY‐anthracene dyads. ChemPhotoChem. doi: 10.1002/cptc.202000191. Full text in Research Archive
• Gederaas, Odrun Arna; Husebye, Harald; Johnsson, Anders Carl G.; Callaghan, Susan & Brunsvik, Anders (2019). In vitro and in vivo effects of HAL on porphyrin production in rat bladder cancer cells (AY27). Journal of Porphyrins and Phthalocyanines. ISSN 1088-4246. 23, p. 813–820. doi: 10.1142/S1088424619500615. Full text in Research Archive
• Shi, Lei; Buchner, Alexander; Pohla, Heike; Pongratz, Thomas; Rühm, Adrian & Zimmermann, Wolfgang [Show all 11 contributors for this article] (2019). Methadone enhances the effectiveness of 5‐aminolevulinic acid‐based photodynamic therapy for squamous cell carcinoma and glioblastoma in vitro. Journal of Biophotonics. ISSN 1864-063X. 12:201800468(10), p. 1–9. doi: 10.1002/jbio.201800468. Full text in Research Archive
• Haug, Markus; Brede, Gaute; Håkerud, Monika; Nedberg, Anne Grete Gargul; Gederaas, Odrun Arna & Flo, Trude Helen [Show all 10 contributors for this article] (2018). Photochemical internalization of peptide antigens provides a novel strategy to realize therapeutic cancer vaccination. Frontiers in Immunology. 9:650, p. 1–14. doi: 10.3389/fimmu.2018.00650. Full text in Research Archive Show summary

  Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here we investigated the potential of PCI as a novel, minimally invasive and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen presenting cells (APCs) in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30-100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

• Holien, Toril; Gederaas, Odrun Arna; Darvekar, Sagar; Christensen, Eidi & Qian, Peng (2018). Comparison Between 8-Methoxypsoralen and 5-Aminolevulinic Acid in Killing T Cells of Photopheresis Patients Ex Vivo. Lasers in Surgery and Medicine. ISSN 0196-8092. 50(5), p. 469–475. doi: 10.1002/lsm.22806. Full text in Research Archive Show summary

  Background and Objective Extracorporeal photopheresis (ECP), an established modality for cutaneous T‐cell lymphoma (CTCL) and graft‐versus‐host disease, involves ex vivo treatment of isolated leukocytes of a patient with the photosensitizing drug 8‐methoxypsoralen (8‐MOP) and ultraviolet‐A (UV‐A) exposure before reinfusion back to the patient. However, 8‐MOP binds to both diseased and normal cells and thus kills both types of the cells after UV‐A illumination with little selectivity. Clinically, this modality gives only partial response in the majority of treated patients. 5‐Aminolevulinic acid (5‐ALA), a precursor of the potent photosensitizer protoporphyrin IX (PpIX), has been shown to selectively induce PpIX in activated T lymphocytes (T cells) and could be an alternative for 8‐MOP. The objectives of this study were to investigate ex vivo 5‐ALA dark toxicity, 5‐ALA‐induced PpIX production, and photodynamic effect on T cells obtained from clinical ECP patients after the treatment of 5‐ALA or 8‐MOP plus a built‐in certified UV‐A source in the commercial Therakos™ Photopheresis System. Materials and Methods Flow cytometry was used to study dark cytotoxic effects of 5‐ALA on human leukocytes, to measure the production of 5‐ALA‐induced PpIX in CD25+ activated T cells from both diluted mononuclear cells and undiluted buffy coat samples of ECP patients and to compare photodynamic effects on CD4+ and CD8+ T cells with 5‐ALA/UV‐A or 8‐MOP/UV‐A. Results No dark toxicity of 5‐ALA on the leukocytes of ECP patients was seen at concentrations up to 10 mM for an incubation of up to 20 hours. 5‐ALA‐induced PpIX was produced more in CD25+ activated T cells than resting T cells in both diluted mononuclear cells and undiluted buffy coat samples, although there was a huge variation of samples from different individual patients. The CD4+ and CD8+ T cells treated with 5‐ALA/UV‐A were killed more than those treated with 8‐MOP/UV‐A. Conclusion These results suggest that 5‐ALA/UV‐A may have the potential for improving the efficacy of ECP. Lasers Surg. Med. 50:469–475, 2018.

• Singh, Rinku; Hals, Ingrid Kathrin; Høgset, Anders; Grill, Valdemar Erik Robert & Gederaas, Odrun Arna (2018). Increased toxicity of amylin (Islet Amyloid Polypeptide) in beta cells induced by photochemical internalization. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 23, p. 218–220. doi: 10.1016/j.pdpdt.2018.06.017. Full text in Research Archive
• Søgaard, Caroline Krogh; Blindheim, Augun; Røst, Lisa Marie; Petrovic, Voin; Nepal, Anala & Bachke, Siri [Show all 12 contributors for this article] (2018). "Two hits - one stone" increased efficacy of cisplatin-based therapies by targeting PCNA's role in both DNA repair and cellular signaling. OncoTarget. 9(65), p. 32448–32465. doi: 10.18632/oncotarget.25963. Full text in Research Archive Show summary

  Low response rate and rapid development of resistance against commonly used chemotherapeutic regimes demand new multi-targeting anti-cancer strategies. In this study, we target the stress-related roles of the scaffold protein PCNA with a cell-penetrating peptide containing the PCNA-interacting motif APIM. The APIM-peptide increased the efficacy of cisplatin-based therapies in a muscle-invasive bladder cancer (MIBC) solid tumor model in rat and in bladder cancer (BC) cell lines. By combining multiple omics-levels, from gene expression to proteome/kinome and metabolome, we revealed a unique downregulation of the EGFR/ERBB2 and PI3K/Akt/mTOR pathways in the APIM-peptide-cisplatin combination treated cells. Additionally, the combination treatment reduced the expression of anti-apoptotic proteins and proteins involved in development of resistance to cisplatin. Concurrently, we observed increased levels of DNA breaks in combination treated cells, suggesting that the APIM-peptide impaired PCNA - DNA repair protein interactions and reduced the efficacy of repair. This was also seen in cisplatin-resistant cells, which notably was re-sensitized to cisplatin by the APIM-peptide. Our data indicate that the increased efficacy of cisplatin treatment is mediated both via downregulation of known oncogenic signaling pathways and inhibition of DNA repair/translesion synthesis (TLS), thus the APIM-peptide hits both nuclear and cytosolic functions of PCNA. The novel multi-targeting strategy of the APIM-peptide could potentially improve the efficacy of chemotherapeutic regiments for treatment of MIBC, and likely other solid tumors.

• Chatzisideri, T; Thysiadis, S; Katsamakas, S; Dalezis, P; Sigala, I & Lazarides, T [Show all 11 contributors for this article] (2017). Synthesis and biological evaluation of a Platinum(II)-c(RGDyK) conjugate for integrin-targeted photodynamic therapy. European Journal of Medicinal Chemistry. ISSN 0223-5234. 141, p. 221–231. doi: 10.1016/j.ejmech.2017.09.058. Full text in Research Archive
• Gederaas, Odrun Arna; Johnsson, Anders Carl G.; Berg, Kristian; Manandhar, Rojlina; Shrestha, Chetana & Skåre, Daniel [Show all 9 contributors for this article] (2017). Photochemical internalization in bladder cancer-development of an orthotopic in vivo model. Photochemical and Photobiological Sciences. ISSN 1474-905X. 16(11), p. 1664–1676. doi: 10.1039/c7pp00176b. Full text in Research Archive
• Helander, Linda; Sharma, Animesh; Krokan, Hans Einar; Plaetzer, Kristjan; Krammer, Barbara & Tortik, Nicole [Show all 9 contributors for this article] (2016). Photodynamic treatment with hexyl-aminolevulinate mediates reversible thiol oxidation in core oxidative stress signaling proteins. Molecular Biosystems. ISSN 1742-206X. doi: 10.1039/c5mb00744e. Full text in Research Archive
• Bogoeva, Vanya; Siksjø, Monica; Sæterbø, Kristin Grendstad; Melø, Thor Bernt; Bjørkøy, Astrid & Lindgren, Mikael [Show all 7 contributors for this article] (2016). Ruthenium porphyrin-induced photodamage in bladder cancer cells. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 14, p. 9–17. doi: 10.1016/j.pdpdt.2016.01.012. Full text in Research Archive
• Alemayehu, Abraham; Day, Nicholas U.; Mani, Tomoyasu; Rudine, Alexander B.; Kolle, Ekaney Thomas & Gederaas, Odrun Arna [Show all 9 contributors for this article] (2016). Gold Tris(carboxyphenyl)corroles as Multifunctional Materials: Room Temperature Near-IR Phosphorescence and Applications to Photodynamic Therapy and Dye-Sensitized Solar Cells. ACS Applied Materials & Interfaces. ISSN 1944-8244. 8(29), p. 18935–18942. doi: 10.1021/acsami.6b04269. Full text in Research Archive
• Gederaas, Odrun Arna; Hauge, Anette; Ellingsen, Pål Gunnar; Berg, Kristian; Altin, Dag & Bardal, Tora [Show all 8 contributors for this article] (2015). Photochemical internalization of bleomycin and temozolomide – in vitro studies on the glioma cell line F98. Photochemical and Photobiological Sciences. ISSN 1474-905X. 14(7), p. 1357–1366. doi: 10.1039/c5pp00144g. Full text in Research Archive
• Baglo, Yan; Qian, Peng; Hagen, Lars; Berg, Kristian; Høgset, Anders & Drabløs, Finn [Show all 7 contributors for this article] (2015). Studies of the photosensitizer disulfonated meso-tetraphenyl chlorin in an orthotopic rat bladder tumor model. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 12(1), p. 58–66. doi: 10.1016/j.pdpdt.2014.12.005. Full text in Research Archive
• Baglo, Yan; Hagen, Lars; Høgset, Anders; Drabløs, Finn; Otterlei, Marit & Gederaas, Odrun Arna (2014). Enhanced efficacy of bleomycin in bladder cancer cells by photochemical internalization. BioMed Research International. ISSN 2314-6133. 14(74). doi: 10.1155/2014/921296. Full text in Research Archive Show summary

  Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI) was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27), as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) and blue light (435 nm). Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not.

• Amundsen, Tore; Sundstrøm, Stein Harald; Buvik, Turid; Gederaas, Odrun & Haaverstad, Rune (2014). Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer. Acta Oncologica. ISSN 0284-186X. 53(3), p. 307–315. doi: 10.3109/0284186X.2013.819996. Full text in Research Archive
• Gederaas, Odrun Arna; Søgaard, Caroline Danielsen; Viset, Trond; Bachke, Siri; Bruheim, Per & Arum, Carl-Jørgen [Show all 7 contributors for this article] (2014). Increased anticancer efficacy of intravesical mitomycin C therapy when combined with a PCNA targeting peptide. Translational Oncology. ISSN 1944-7124. 7(6), p. 812–823. doi: 10.1016/j.tranon.2014.10.005. Full text in Research Archive Show summary

  Non–muscle-invasive bladder cancers (NMIBCs) are tumors confined to the mucosa or the mucosa/submucosa. An important challenge in treatment of NMIBC is both high recurrence and high progression rates. Consequently, more efficacious intravesical treatment regimes are in demand. Inhibition of the cell’s DNA repair systems is a new promising strategy to improve cancer therapy, and proliferating cell nuclear antigen (PCNA) is a new promising target. PCNA is an essential scaffold protein in multiple cellular processes including DNA replication and repair. More than 200 proteins, many involved in stress responses, interact with PCNA through the AlkB homologue 2 PCNA-interacting motif (APIM), including several proteins directly or indirectly involved in repair of DNA interstrand crosslinks (ICLs). In this study, we targeted PCNA with a novel peptide drug containing the APIM sequence, ATX- 101, to inhibit repair of the DNA damage introduced by the chemotherapeutics. A bladder cancer cell panel and two different orthotopic models of bladder cancer in rats, the AY-27 implantation model and the dietary BBN induction model, were applied. ATX-101 increased the anticancer efficacy of the ICL-inducing drug mitomycin C (MMC), as well as bleomycin and gemcitabine in all bladder cancer cell lines tested. Furthermore, we found that ATX-101 given intravesically in combination with MMC penetrated the bladder wall and further reduced the tumor growth in both the slow growing endogenously induced and the rapidly growing transplanted tumors. These results suggest that ATX-101 has the potential to improve the efficacy of current MMC treatment in NMIBC.

• Helander, Linda; Krokan, Hans Einar; Johnsson, Anders Carl G.; Gederaas, Odrun Arna & Plaetzer, Kristjan (2014). Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro. Journal of Biomedical Optics. ISSN 1083-3668. 19:088002(8). doi: 10.1117/1.JBO.19.8.088002. Full text in Research Archive Show summary

  Abstract. Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT624 induced more apoptosis than HAL-PDT410 and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

• Baglo, Yan; Gabrielsen, Mari; Sylte, Ingebrigt & Gederaas, Odrun Arna (2013). Homology Modeling of Human <gamma>-Butyric Acid Transporters and the Binding of Pro-drugs 5-Aminolevulinic Acid and Methyl Aminolevulinic Acid used in Photodynamic Therapy. PLOS ONE. 8(6). doi: 10.1371/journal.pone.0065200. Full text in Research Archive Show summary

  Photodynamic therapy (PDT) is a safe and effective method currently used in the treatment of skin cancer. In ALA-based PDT, 5-aminolevulinic acid (ALA), or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizer protoporphyrin IX (PpIX). Activation of PpIX by light causes the formation of reactive oxygen species (ROS) and toxic responses. Studies have indicated that ALA and its methyl ester (MAL) are taken up into the cells via c-butyric acid (GABA) transporters (GATs). Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverse side effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes were constructed using three x-ray crystal structures of the homologous leucine transporter (LeuT) as templates. Binding of the native substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands into the central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs) of the putative substrate translocation pathway of each subtype were calculated using the outward-open and inward-open homology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3 and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. in outward-open conformations). Such differences may be exploited for development of inhibitors that selectively target specific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can be used to reduce ALA-induced pain.

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• Swaminathan, Priyanka; Sundnes, Marikken L; Lindgren, Mikael; Gederaas, Odrun Arna; Klingstedt, Thérese & Nyström, Sofie [Show all 9 contributors for this article] (2024). Hyperspectral imaging of amyloid asynuclein(asyn) in HEK293 cells using Luminescent conjugated oligothiophenes(LCOs). Full text in Research Archive
• Swaminathan, Priyanka; Lindgren, Mikael & Gederaas, Odrun Arna (2024). Use of in-vitro cell models and protein fluorescent markers for studying amyloid related diseases. Full text in Research Archive
• Sundnes, Marikken L; Swaminathan, Priyanka; Gederaas, Odrun Arna; Lindgren, Mikael; Klingstedt, Thérese & Hellstrand, Ebba [Show all 10 contributors for this article] (2023). Hyperspectral microscopy and ligand screening of TTR amyloid fibrils. Full text in Research Archive
• Swaminathan, Priyanka; Sundnes, Marikken L; Vindstad, Benedikte; Gederaas, Odrun Arna; Lindgren, Mikael & Klingstedt, Thérese [Show all 10 contributors for this article] (2023). Use of in-vitro cell-models in understanding amyloidosis. Full text in Research Archive
• Gederaas, Odrun Arna; Høgset, Anders & Lindgren, Olof Mikael (2023). In vivo and in vitro models for photodynamic therapy by using novel photosensitizers. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 41, p. 103435–103435. doi: 10.1016/j.pdpdt.2023.103435. Full text in Research Archive
• Gederaas, Odrun Arna (2021). Photodynamic Therapy (PDT)- in vitro and in vivo studies using novel photosensitizers. Full text in Research Archive
• Gederaas, Odrun Arna (2020). Prosperities of a novel photosensitive molecule. Full text in Research Archive
• Gederaas, Odrun Arna & Hagen, Lars (2020). Drug delivery and endosomal drug quantification of Doxorubicin post photochemical internalization. Full text in Research Archive
• Gederaas, Odrun Arna; Callaghan, Susan; Vindstad, Benedikte E.; Flanaghan, Keith J.; Melø, Thor Bernt & Sæterbø, Kristin G. [Show all 8 contributors for this article] (2020). Photobiological studies on a novel lead BODIPY-anthracene dyad for bladder cancer therapy. Full text in Research Archive
• Gederaas, Odrun Arna; Sørensen, Andreas S.; Lindgren, Mikael & Hoff, Bård Helge (2020). Prosperities of a novel and photosensitive molecule. Full text in Research Archive
• Gederaas, Odrun Arna; Johnsson, Anders; Berg, Kristian; Manandhar, Rojlina; Shrestha, Chetana & Skåre, Daniel [Show all 9 contributors for this article] (2019). Effects of Photochemical Internalization (PCI) - Bladder Cancer, in vitro and in vivo. Full text in Research Archive
• Gederaas, Odrun Arna (2019). Fotodynamisk radioterapi for blærekreft. Full text in Research Archive
• Gederaas, Odrun Arna; Johnsson, Anders Carl G.; Berg, Kristian; Manandhar, Rojlina; Shrestha, Chetana & Skåre, Daniel [Show all 9 contributors for this article] (2019). Photochemical Internalization (PCI) - Bladder Cancer. Full text in Research Archive
• Gederaas, Odrun Arna; Granja, Andreia; Hansen, Tom Andre; Lindgren, Mikael; Pinheiro, M. & Sousa, C. T. [Show all 7 contributors for this article] (2019). Assessing the influence of gold nanoparticles in photodynamic therapy using singlet oxygen sensitizers. Full text in Research Archive
• Gederaas, Odrun Arna (2019). Interdisiplinary research including pharmacy. Full text in Research Archive
• Gederaas, Odrun Arna; Saidshahagha, Orjahan; Høgset, Anders & Hagen, Lars (2019). Quantification of Doxorubicin in endosomes of rat bladder cancer cells (AY27) post photochemical internalization. Full text in Research Archive
• Gederaas, Odrun Arna; Johnsson, Anders Carl G.; Høgset, Anders; Hjelde, Astrid & Lindgren, Mikael (2019). Novel Technologies by Photodynamic Therapy (PDT). Full text in Research Archive
• Gederaas, Odrun Arna (2018). Photodynamic therapy (PDT) - in vitro and in vivo experiments. Full text in Research Archive
• Gederaas, Odrun Arna; Bogoeva, Vanya; Johnsson, Anders Carl G.; Berg, Kristian; Høgset, Anders & Lindgren, Mikael (2018). Photophysical observations on tetrapyrroles during in vitro and in vivo PDT. Full text in Research Archive
• Haug, Markus; Brede, Gaute; Håkerud, Monika; Nedberg, A; Gederaas, Odrun Arna & Edwards, Victoria Tudor [Show all 10 contributors for this article] (2018). Photochemical internalization as a novel strategy to realize therapeutic cancer peptide vaccination. Full text in Research Archive
• Gederaas, Odrun Arna; Einrem, Rune Finsås; Alemayehu, Abraham; Bogoeva, Vanya; Ghosh, Abhik & Lindgren, Mikael (2018). Photodynamic therapy using corroles and ruthenium porphyrins. Full text in Research Archive
• Gederaas, Odrun Arna (2018). Psoralens and porphyrin precursors in medical treatment. Full text in Research Archive
• Gederaas, Odrun Arna; Holien, Toril; Darvekar, Sagar; Christensen, Eidi & Qian, Peng (2018). Comparison between 8-methoxypsoralen and 5-aminolevulinic acid in killing T cells of photopheresis patients ex vivo. Full text in Research Archive
• Gederaas, Odrun Arna (2018). Interdisiplinary research including pharmacy. Full text in Research Archive
• Gederaas, Odrun Arna (2017). Photodynamic Therapy – in vitro and in vivo studies using novel photosensitizers and cancer cells. Full text in Research Archive
• Gederaas, Odrun Arna; Sharma, Animesh; Bogoeva, Vanya; Mbarak, Saide; Kanamazina, Yusuf & Sporsheim, Bjørnar [Show all 9 contributors for this article] (2017). The proteome of endosomes after Bleomycine-mediated photochemical internalization on rat bladder cancer cells. Full text in Research Archive
• Gederaas, Odrun Arna (2017). Orthotopic glioma model and bladder cancer models on rats-suitable tools for PDT and PCI. Full text in Research Archive
• Gederaas, Odrun Arna (2017). PHOTOBIOLOGY - How to use light in treatment and research. Full text in Research Archive
• Gederaas, Odrun Arna (2017). Photodynamic Therapy (PDT) – novel technologies. Full text in Research Archive
• Gederaas, Odrun Arna (2017). Photochemical techniques available for BioBrilloun members. Full text in Research Archive
• Gederaas, Odrun Arna; Johnsson, Anders Carl G.; Berg, Kristian; Manandhar, Rojlina; Shresta, Chetana & Skåre, Daniel [Show all 9 contributors for this article] (2017). Photochemical internalization in bladder cancer – development of an orthotopic in vivo model. Full text in Research Archive
• Søgaard, Caroline Danielsen; Petrovic, Voin; Blindheim, Augun; Gederaas, Odrun Arna; Arum, Carl-Jørgen & Otterlei, Marit (2016). PCNA-targeting APIM-peptide alters response to DNA damage in human bladder cancer cells on a signaling level. Full text in Research Archive
• Gederaas, Odrun Arna (2016). Photodynamic Therapy (PDT)-novel technologies. Full text in Research Archive
• Gederaas, Odrun Arna & Qian, Peng (2016). Extracorporeal photopheresis - today and in the future. Full text in Research Archive
• Gederaas, Odrun Arna (2016). Photodynamic Therapy (PDT) - Some examples. Full text in Research Archive
• Gederaas, Odrun Arna; Johnsson, Anders Carl G.; Berg, Kristian; Manandhar, Rojlina; Shresta, Chetana & Skåre, Daniel [Show all 9 contributors for this article] (2016). Photochemical Internalization in bladder cancer-developement of an orthotopic in vivo model. Full text in Research Archive
• Gederaas, Odrun Arna (2016). Rapport fra opponent Ass. Professor. Odrun Gederaas, NTNU, vedr. PhD avhandling til Jan Capar, UiT: «Synthesis of Sterically Hindered Macrocyclic Ligands via Demetalation of Metallocorroles». Full text in Research Archive
• Gederaas, Odrun Arna; Siksjø, Monica; Sæterbø, Kristin G.; Melø, Thor Bernt; Bjørkøy, Astrid & Lindgren, Mikael [Show all 7 contributors for this article] (2016). Ruthenium porphyrin-induced photodamage in bladder cancer cells. Full text in Research Archive
• Gederaas, Odrun Arna (2016). Technologies actual for photodyamic therapy and photochemical internalization. Full text in Research Archive
• Gederaas, Odrun Arna (2016). Enhanced efficacy of Bleomycin in bladder cancer cells by Photochemical Internalization (PCI). Full text in Research Archive
• Gederaas, Odrun Arna (2016). Research and partnership depending on university structures. Photodynamic Therapy with focus on Photopheresis. Full text in Research Archive
• Gederaas, Odrun Arna (2016). Photodynamic Therapy (PDT) by using 5-aminolevululinic (ALA) based photosensitizers. Full text in Research Archive
• Gederaas, Odrun Arna (2015). "Bruk av lys i kreftbehandling og forskning". Full text in Research Archive
• Mathisen, Georg & Gederaas, Odrun Arna (2015). "Lyser opp og opplyser". Seminar arrangert av Odrun Gederaas, IKM (NTNU) med finansiering fra Forskningsrådet. [Journal]. Vedr. Seminar på Rockheim, Tr.heim. 24.9.2015. Internett. Full text in Research Archive
• Bogoeva, Vanya; Lindgren, Mikael; Siksjø, Monica; Sæterbø, Kristin Grendstad; Melø, Thor Bernt & Bjørkøy, Astrid [Show all 7 contributors for this article] (2015). Photodynamic therapy by using Ruthenium porphyrin on the AY27 rat bladder cancer cell line. Full text in Research Archive Show summary

  Abstract. Photodynamic therapy is a noninvasive treatment of solid tumors, using photosensitisers, which after activation by light produce reactive oxygen species that selectively destroy target cells. Current focus highlights the photophysical characteristics and the effects of the treatment of the 2,3,7,8,12,13,17,18-OCTAETHYL-21H, 23H-PORPHINE RUTHENIUM(II) CARBONYL (RuP) upon rat bladder cancer cells (Ay27). Photophysical properties of the porphyrin were assessed using: time resolved spectroscopy, life time measurements. The obtained results have shown that RuP is an excellent photosensitizer, suitable for Photodynamic therapy application (PDT). In vitro experiments indicated that the phototoxic effect of RuP is significantly higher, after irradiation (453nm) with RuP upon Ay27, compared to the cytotoxic effect (due to non-irradiation, without light). Confocal microscopy experiments also confirmed higher apoptotic effect of RuP, after irradiation. Additionally, we found that the effect of RuP is higher than the effect of the conventional chemotherapy drug cisplatin, both evaluated by MTT assay. In conclusion, RuP significantly enhanced its phototoxic effect upon AY27 cells, which indicated a potential for further investigations focused on selective treatment of non-suscle invasive bladder cancer.

• Gederaas, Odrun Arna; Siksjø, Monica; Mettra, Bastien; Monnereau, Cyrille; Egeberg, Kjartan Wøllo & Andraud, Chantal [Show all 7 contributors for this article] (2015). Photophysics and in cellulo studies of novel light sensitive chromophores with potential application in Photodynamic therapy. Full text in Research Archive Show summary

  Photophysics and in cellulo studies of novel light sensitive chromophores with potential application in Photodynamic therapy Odrun A. Gederaas1, Monica Siksjø2, Bastien Mettra3, Cyrille Monnereau3, Kjartan W. Egeberg1, Chantal Andraud3 and Mikael Lindgren2 1) Department of Cancer Research and Molecular Medicine, University of Science and Technology, N-7489 Trondheim, Norway 2) Department of Physics, N-7491 Trondheim, Norway 3) CNRS UMR 5182, Université Lyon 1, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France Hydrophilic and hydrophobic chromophores are taken up by cells and are usually located in cellular lipid membranes but accumulate in different compartments of the cell. The aim of this study was to investigate biophysical properties of four light sensitive chromophores1,2 for bioimaging applications, and to test their efficiency as potential photosensitizer in photodynamic therapy (PDT). This is a general statement and not verified stringently for all of the probes. The chromophores where all proven to accumulate within tested F98 glioma and CHO-K1 hamster ovary cells. For one of the chromophores (Ant-Poly Imidazole), the polycationic nature of the side chain helped its permeation inside the cell nucleus. Then, characterizations of light induced cell death and DNA damage (Comet assay) were performed using cell survival assay (MTT) and confocal microscopy. Our studies demonstrate structural and morphological changes within the two cell lines upon light/no light treatment after sensitizer or chromophore incubation. Quite surprisingly, one of the hydrophilic anthracene compounds (Ant-Poly Imidazole) although not specifically designed to that end, showed promising results for PDT with accelerated cell death upon illumination compared to the other hydrophilic anthracene compound (Ant-PHEA). Transient absorption measurements revealed a long lived triplet state in one of the tested bromobenzene derivative (DBB2-OAc). The latter also showed generation of singlet oxygen from transient luminescence measurement in the singlet oxygen phosphorescence band, making it a promising candidate for type II PDT. This project is an ongoing collaborating study between ENS Lyon, France, and NTNU, Norway. 1. Monnereau C. et al., New. J. Chem., 2012, 36, 2328-2333. 2. Gallavardin T. et al., Chem. Commun., 2012, 48,1689-169.

• Gederaas, Odrun Arna (2015). Hva har lyset betydd for mennesket ? Full text in Research Archive
• Gederaas, Odrun Arna; Hauge, Anette; Ellingsen, Pål Gunnar; Berg, Kristian; Altin, Dag & Bardal, Tora [Show all 8 contributors for this article] (2015). Photochemical internalization of bleomycin and temozolomide-in vitro on the glioma cell line F98. Full text in Research Archive
• Gederaas, Odrun Arna; Siksjø, Monica; Mettra, Bastien; Monnereau, Cyrille; Egeberg, Kjartan Wøllo & Andreau, Chanthal [Show all 7 contributors for this article] (2015). "Anthracene studies in photodynamic therapy and other ongoing projects". Full text in Research Archive Show summary

  Anthracene studies in photodynamic therapy and other ongoing projects. Odrun A. Gederaas1, Monica Siksjø2, Bastien Mettra3, Cyrille Monnereau3, Kjartan W. Egeberg1, Chantal Andraud3 and Mikael Lindgren2 1) Department of Cancer Research and Molecular Medicine, University of Science and Technology, N-7489 Trondheim, Norway 2) Department of Physics, N-7491 Trondheim, Norway 3) CNRS UMR 5182, Université Lyon 1, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France Hydrophilic and hydrophobic chromophores are taken up by cells and are usually located in cellular lipid membranes but accumulate in different compartments of the cell. The aim of this study was to investigate biophysical properties of four light sensitive chromophores1,2 for bioimaging applications, and to test their efficiency as potential photosensitizer in photodynamic therapy (PDT). This is a general statement and not verified stringently for all of the probes. The chromophores where all proven to accumulate within tested F98 glioma and CHO-K1 hamster ovary cells. For one of the chromophores (Ant-Poly Imidazole), the polycationic nature of the side chain helped its permeation inside the cell nucleus. Then, characterizations of light induced cell death and DNA damage (Comet assay) were performed using cell survival assay (MTT) and confocal microscopy. Our studies demonstrate structural and morphological changes within the two cell lines upon light/no light treatment after sensitizer or chromophore incubation. Quite surprisingly, one of the hydrophilic anthracene compounds (Ant-Poly Imidazole) although not specifically designed to that end, showed promising results for PDT with accelerated cell death upon illumination compared to the other hydrophilic anthracene compound (Ant-PHEA). Transient absorption measurements revealed a long lived triplet state in one of the tested bromobenzene derivative (DBB2-OAc). The latter also showed generation of singlet oxygen from transient luminescence measurement in the singlet oxygen phosphorescence band, making it a promising candidate for type II PDT. This project is an ongoing collaborating study between ENS Lyon, France, and NTNU, Norway. 1. Monnereau C. et al., New. J. Chem., 2012, 36, 2328-2333. 2. Gallavardin T. et al., Chem. Commun., 2012, 48,1689-169.

• Gederaas, Odrun Arna; Siksjø, Monica; Sæterbø, Kristin Grendstad; Melø, Thor Bernt; Bjørkøy, Astrid & Lindgren, Mikael [Show all 7 contributors for this article] (2015). Photochemical reactions after nano particle stimulating. In vitro and in vivo studies. Full text in Research Archive Show summary

  Photochemical reactions after nano particle stimulating. In vitro and in vivo studies Odrun A. Gederaasa, Monica Siksjøb, Kristin G. Sæterbøb, Thor Bernt Meløb, Astrid Bjørkøyb, Mikael Lindgrenb,c, Vanya Bogoevad a) Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7491 Trondheim, Norway b) Department of Physics, Norwegian University of Science and Technology, N-7491 Trondheim, Norway c) Department of Physics, Chemistry and Biology, Linköping University, SE-58183 Linköping, Sweden d) Department Molecular Biology of Cell Cycle Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. “G. Bonchev” Str., Bl. 21, Sofia 1113, Bulgaria Abstract Photodynamic therapy (PDT) is a noninvasive treatment for solid malignant and flat tumors. Both endogen and exogen added photosensitizers1 were used in vitro and in vivo studies according to development of new treatment strategies. The light activated sensitizers catalyze photochemical reactions that produce reactive oxygen species which can cause cancer cell death. The photophysical properties of the photosensitizer ruthenium (II) porphyrin (RuP) have been investigated, along with its PDT efficiency onto rat bladder cancer cells (AY27)2. Optical spectroscopy verified that RuP is capable to activate singlet oxygen via blue and red absorption bands and inter system crossing (ISC) to the triplet state3. In vitro experiments on AY27 indicated increased photo-toxicity of RuP (20 µM, 18 h incubation) after cell illumination (at 435 nm, 13 mW/cm2), as a function of blue light exposure. Cell survival fraction was significantly reduced to 14% after illumination (20 min), RuP (20 µM), whereas the “dark toxicity” of RuP (20 µM) was 83%. Structural and morphological changes of cells were observed, due to RuP accumulation, as well as light-dependent cell death, was registered by confocal microscopy. Flow cytometry verified that PDT-RuP (50 µM) triggered significant photo-induced cellular destruction with photoxicity of (93% ±0.9%). Interestingly, the present investigation of RuP-PDT showed that the dominating mode of cell death is necrosis. RuP “dark toxicity” compared to the conventional chemotherapy drug cisplatin, showed higher toxicity, both evaluated by MTT assay (24 h). In conclusion, the present investigation shows that RuP induces cell damage of bladder cancer cells. 1. Gederaas O. A. et al., Photochem. Photobiol. Sci. 2015; 14(7); 1357-6 2. Bogoeva V. et al., J Photochem Photobiol B. 2015(20); 153:276-280 3. Glimsdal E. et al., J Phys. Chem A. 2009(113); 3311-3320

• Gederaas, Odrun Arna (2014). "In vitro and in vivo models in PDT", related to EU application "Innovative Training Networks (ITN): Call: H2020-MSCA-ITN-2015. Full text in Research Archive
• Gederaas, Odrun Arna & Høgset, Anders (2014). Behandling av ulike kreftformer på et tidlig stadium. Full text in Research Archive
• Gederaas, Odrun Arna; Berg, Kristian & Hauge, Anette (2014). Glioma rat cancer studies using PCI technology. Full text in Research Archive
• Gederaas, Odrun Arna; Høgset, Anders; Berg, Kristian; Lindgren, Mikael & Siksjø, Monica (2014). Intracellular studies on rat glioma cancer cell line using novel chromophores. Full text in Research Archive
• Gederaas, Odrun Arna (2014). Glioma rat cancer studies using PCI technology. Full text in Research Archive
• Gederaas, Odrun Arna (2014). "Intracellular studies on rat glioma cancer cell line using novel chromophores". Mandagsmøte, IKM, NTNU. Full text in Research Archive
• Gederaas, Odrun Arna (2014). Localization and photodynamic therapy of chromophores targeted for cancer cells. Full text in Research Archive
• Gederaas, Odrun Arna; Siksjø, Monica & Lindgren, Mikael (2014). Prosjektmøte med samarbeidspartnere for masterstudent Monica Siksjø: Tittel på oppgave: "Optical microscopy studies of localization of PDT chromophores in glioma cells". Full text in Research Archive
• Gederaas, Odrun Arna (2014). 1. opponent til PhD Thesis ved Naval Sekkat, University of Geneve, 26. Sept.2014 Tittle: "Optimization of Proteolytically Induced Photosensitizers for Fluorescence Imaging and Photodynamic Therapy". Full text in Research Archive
• Gederaas, Odrun Arna (2014). Seminar, Norwegian Graduate School in Structural Biology (Biostruct), Jægtvollen. Planlegging av videre prosjekter med foredragsholdere og arrangører (O. Gederaas har tidligere vert en del av BioStuct sitt styre). Full text in Research Archive
• Gederaas, Odrun Arna (2014). Biostruct kurs, Univ. i Tromsø. "Structur guided drug discovery and design". Full text in Research Archive
• Siksjø, Monica; Mettra, Bastien; Hauge, Anette; Ellingsen, Pål; Høgset, Anders & Egeberg, Kjartan Wøllo [Show all 10 contributors for this article] (2013). Localization and photodynamic therapy of chromophores targeted for cancer cells. Full text in Research Archive
• Gederaas, Odrun (2013). Kreftceller lyser opp og dør. Full text in Research Archive
• Baglo, Yan; Gabrielsen, Mari; Sylte, Ingebrigt & Gederaas, Odrun Arna (2013). Homology Modeling of Human <gamma>-Butyric Acid Transporters and the Binding of Pro-drugs 5-Aminolevulinic Acid and Methyl Aminolevulinic Acid used in Photodynamic Therapy. Full text in Research Archive
• Hansen, Tom Andre; Lindgren, Mikael & Gederaas, Odrun Arna (2018). Investigation of some compounds and gold nanoparticles for photodynamic therapy. Norges teknisk-naturvitenskapelige universitet. Full text in Research Archive Show summary

  In this thesis several chemical compounds for possible use as photosensitizers (PS) in photodynamic therapy (PDT) have been investigated. First a photophysical characterization was performed using different spectroscopic techniques. With these methods the absorption, fluorescence, fluorescence lifetime and quantum yield, triplet excited state absorption and singlet oxygen luminescence, were quantified. Furthermore, experiments using cancer cell models were carried out to investigate possible compounds for PDT. The compounds which have been characterized can be divided into two groups; three different protoporphyrins and three dye compounds, all known to produce singlet oxygen. Among the protoporphyrins, Protoporphyrin A showed higher absorption, fluorescence and singlet oxygen production and lifetime compared to Protoporphyrin B and Protoporphyrin IX. Comparing the three singlet oxygen producing compounds, both eosin B and perinaphtenone showed very weak fluorescence, while erythrosin B had a much stronger fluorescence. Perinaphtenone yielded a better singlet oxygen production and longer singlet oxygen lifetime while eosin B showed no singlet oxygen luminescence. The cell lines AY27 (cancer from rat bladder) and WiDr (cancer from human colon) were used in PDT experiments. The WiDr cells were used in photobleaching experiments containing cells treated with Protoporphyrin A or Protoporphyrin B. The exposure time of blue light (412 nm) ranged from no light up to 600 seconds. An investigation of the addition of gold nanoparticles to erothrysin B, in order to enhance the effect of PDT, was performed after initial photophysical characterization. The toxicity of gold nanoparticles were determined by checking the cell viability with the use of a MTT-assay. The results from this assay were studied to obtain a concentration of gold nanoparticles which were added to erythrosin B incombination by light treatment (532 nm) of AY27 cells. This yielded no significant difference between cells treated with an addition of gold nanoparticles, as opposed to those without.

• Moe, Nogaye; Hagen, Lars & Gederaas, Odrun Arna (2018). Bleomycin in endosomes after photochemical internalization (PCI) in bladder cancer cells (AY27). Nogaye Moe. Full text in Research Archive
• Singh, Rinku; Grill, Valdemar Erik Robert; Hals, Ingrid Kathrin & Gederaas, Odrun Arna (2018). On the susceptibility and adaptability of beta cells to stressful conditions: effects of nutrient scarcity, hyperoxia and internalization of amylin. Norges teknisk-naturvitenskapelige universitet. ISSN 9788232628537. Full text in Research Archive
• Orjahan, Sayed; Gederaas, Odrun Arna & Hagen, Lars (2017). Endosomal uptake of Doxorubicin in cancer cells after photochemical internalization. Orjahan Sayed. Full text in Research Archive
• Kanamazina, Yusuf; Gederaas, Odrun Arna & Hagen, Lars (2016). Proteomic analysis of endosomes after photochemical internalization - establishment of new protocol for rat bladder cancer cell line (AY27). Tapir Akademisk Forlag. Full text in Research Archive
• Saide, Mbarak; Gederaas, Odrun Arna & Hagen, Lars (2016). Photochemical internalization by cancer cell lines from rat glioma(F98) and bladder (AY27) and its proteome analyses. Tapir Akademisk Forlag. Full text in Research Archive
• Helander, Linda; Krokan, Hans Einar; Gederaas, Odrun Arna; Johnsson, Anders Carl G. & Chen, Duan (2015). Hexylaminolevulinate Photodynamic Treatment of Cancer Cell Lines. PhD Thesis. Tapir Akademisk Forlag. Full text in Research Archive

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