Alf Kristian Berg

• Longva, Ane Sager; Berg, Kristian & Weyergang, Anette (2023). Light-enhanced VEGF<inf>121</inf>/rGel induce immunogenic cell death and increase the antitumor activity of αCTLA4 treatment. Frontiers in Immunology. ISSN 1664-3224. 14. doi: 10.3389/fimmu.2023.1278000.
• Régagnon, Théo; Bugnicourt-Moreira, Loic; Ravaz, Romain; Idlas, Pierre; Ramousset, Lilly & Kouassi, Marie-Carole [Vis alle 11 forfattere av denne artikkelen] (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.
• Panagiotakis, Stylianos; Mavroidi, Barbara; Athanasopoulos, Alexandros; Gonçalves, Antonio Ricardo; Bugnicourt-Moreira, Loïc & Regagnon, Theo [Vis alle 15 forfattere av denne artikkelen] (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.
• 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. ISSN 2076-3921. 10:1149(7), s. 1–12. doi: 10.3390/antiox10071149. Fulltekst i vitenarkiv
• Romena, Gabrielle; Nguyen, Lina; Berg, Kristian; Madsen, Steen J. & Hirschberg, Henry (2021). Enhanced gene transfection of macrophages by photochemical internalization: Potential for gene-directed enzyme prodrug therapy of gliomas. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 33. doi: 10.1016/j.pdpdt.2020.102098.
• Engebraaten, Olav; Yau, Christina; Berg, Kristian; Borgen, Elin; Garred, Øystein & Berstad, Maria Elisabeth Brandal [Vis alle 11 forfattere av denne artikkelen] (2021). RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer. Nature Communications. ISSN 2041-1723. 12(1). doi: 10.1038/s41467-021-26018-z. Fulltekst i vitenarkiv
• Mastrangelopoulou, Maria; Grigalavicius, Mantas; Henriksen-Raabe, Tine Therese; Skarpen, Ellen; Juzenas, Petras & Qian, Peng [Vis alle 8 forfattere av denne artikkelen] (2020). Predictive biomarkers for 5-ALA-PDT can lead to personalized treatments and overcome tumor-specific resistances. Cancer Reports. ISSN 2573-8348. s. 1–16. doi: 10.1002/cnr2.1278.
• Nguyen, Jimmi; Madsen J, Steen; 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.
• Li, Xue; Salzano, Giuseppina; Qiu, Jingwen; Ménard, Mathilde; Berg, Kristian & Theodossiou, Theodossis [Vis alle 8 forfattere av denne artikkelen] (2020). Drug-Loaded Lipid-Coated Hybrid Organic-Inorganic “Stealth” Nanoparticles for Cancer Therapy. Frontiers in Bioengineering and Biotechnology. ISSN 2296-4185. doi: 10.3389/fbioe.2020.01027.
• Nguyen, Lina; Potma, Eric O.; Le, Jimmy N.; Johnson, Julie; Romena, Gabrielle & Qian, Peng [Vis alle 8 forfattere av denne artikkelen] (2020). Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier. Lasers in Medical Science. ISSN 0268-8921. doi: 10.1007/s10103-020-03140-w.
• Jerjes, Waseem; Theodossiou, Theodossis; Hirschberg, Henry; Høgset, Anders; Weyergang, Anette & Selbo, Pål Kristian [Vis alle 9 forfattere av denne artikkelen] (2020). Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research. Journal of Clinical Medicine. ISSN 2077-0383. 9(2). doi: 10.3390/jcm9020528. Fulltekst i vitenarkiv
• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Arous, Delmon; Juzeniene, Asta; Ménard, Mathilde & Skarpen, Ellen [Vis alle 8 forfattere av denne artikkelen] (2020). Photodynamic efficacy of cercosporin in 3D tumor cell CCultures. Photochemistry and Photobiology. ISSN 0031-8655. 96(3), s. 699–707. doi: 10.1111/php.13257. Fulltekst i vitenarkiv
• Wong, Judith Jing Wen; Berstad, Maria Elisabeth Brandal; Fremstedal, Ane Sofie Viset; Berg, Kristian; Patzke, Sebastian & Sørensen, Vigdis [Vis alle 9 forfattere av denne artikkelen] (2020). Photochemically-induced release of lysosomal sequestered sunitinib: Obstacles for therapeutic efficacy. Cancers. ISSN 2072-6694. 12(2). doi: 10.3390/cancers12020417. Fulltekst i vitenarkiv
• Peng, Wei; de Bruijn, Henriette S.; Ten Hagen, Timo L. M.; Berg, Kristian; Roodenburg, Jan L. N. & van Dam, Go M. [Vis alle 8 forfattere av denne artikkelen] (2020). In-vivo optical monitoring of the efficacy of epidermal growth factor receptor targeted photodynamic therapy: The effect of fluence rate. Cancers. ISSN 2072-6694. 12(1). doi: 10.3390/cancers12010190.
• Peng, Weiming; de Bruijn, Henriette S.; ten Hagen, Timo L. M.; van Dam, Go M.; Roodenburg, Jan L. N. & Berg, Kristian [Vis alle 8 forfattere av denne artikkelen] (2020). Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model. Photochemistry and Photobiology. ISSN 0031-8655. 96(3), s. 708–717. doi: 10.1111/php.13267.
• Jerjes, Waseem; Hamdoon, Zaid; Berg, Kristian; Høgset, Anders & Hopper, Colin (2020). Apparent Complete Response of a Treatment Refractory and Recurrent Squamous Cell Carcinoma Lesion to Photochemical Internalization: A Clinical Case Study. Photochemistry and Photobiology. ISSN 0031-8655. doi: 10.1111/php.13210.
• Sun, Chung-Ho; Berg, Kristian & Hirschberg, Henry (2019). Photochemical Internalization Enhanced Nonviral Suicide Gene Therapy. Methods in molecular biology. ISSN 1064-3745. 1895, s. 165–176. doi: 10.1007/978-1-4939-8922-5_13.
• Theodossiou, Theodossis; Ali, Muhammad; Grigalavicius, Mantas; Grallert, Beata; Dillard, Pierre & Schink, Kay Oliver [Vis alle 12 forfattere av denne artikkelen] (2019). Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT-tamoxifen hybrid therapy . NPJ breast cancer. ISSN 2374-4677. doi: 10.1038/s41523-019-0108-8.
• Olsen, Cathrine Elisabeth; Chung, Lawrence H.; Weyergang, Anette; Berg, Kristian; Vallera, Daniel A. & Rosenblum, Michael G. [Vis alle 7 forfattere av denne artikkelen] (2019). Design, Characterization, and Evaluation of scFvCD133/rGelonin: A CD133-Targeting Recombinant Immunotoxin for Use in Combination with Photochemical Internalization. Journal of Clinical Medicine. ISSN 2077-0383. 9(1). doi: 10.3390/jcm9010068.
• Jerjes, Waseem; Hamdoon, Zaid; Berg, Kristian; Høgset, Anders & Hopper, Colin (2019). Recurrent chondroblastic osteosarcoma of the right mandible subjected to photochemical internalization. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 27, s. 288–290. doi: 10.1016/j.pdpdt.2019.06.018.
• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Berg, Kristian; Arous, Delmon; Ménard, Mathilde & Henriksen-Raabe, Tine Therese [Vis alle 12 forfattere av denne artikkelen] (2019). Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production. Nature Communications. ISSN 2041-1723. 10(1). doi: 10.1038/s41467-019-12042-7. Fulltekst i vitenarkiv
• Shin, Diane; Nguyen, Lina; T Le, Mai; Ju, David; N Le, Jimmy & Berg, Kristian [Vis alle 7 forfattere av denne artikkelen] (2019). The effects of low irradiance long duration photochemical internalization on glioma spheroids. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 26, s. 442–447. doi: 10.1016/j.pdpdt.2019.05.005.
• Shin, Diane; Christie, Catherine; Ju, David; Nair, Rohit Kumar; Molina, Stephanie & Berg, Kristian [Vis alle 9 forfattere av denne artikkelen] (2018). Photochemical internalization enhanced macrophage delivered chemotherapy. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 21, s. 156–162. doi: 10.1016/j.pdpdt.2017.12.002.
• Weyergang, Anette; Fremstedal, Ane Sofie Viset; Skarpen, Ellen; Qian, Peng; Mohamedali, Khalid A. & Eng, Marius Strømbo [Vis alle 10 forfattere av denne artikkelen] (2018). Light-enhanced VEGF121/rGel: A tumor targeted modality with vascular and immune-mediated efficacy. Journal of Controlled Release. ISSN 0168-3659. 288, s. 161–172. doi: 10.1016/j.jconrel.2018.09.005.
• Eng, Marius Strømbo; Kaur, Jagdip; Prasmickaite, Lina; Engesæter, Birgit Øvstebø; Weyergang, Anette & Skarpen, Ellen [Vis alle 12 forfattere av denne artikkelen] (2018). Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins. Photochemical and Photobiological Sciences. ISSN 1474-905X. 17(5), s. 539–551. doi: 10.1039/c7pp00358g.
• 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. s. 1–10. doi: 10.1111/php.12997.
• Nair, Rohit Kumar; Christie, Catherine; Ju, David; Shin, Diane; Pomeroy, Aftin & Berg, Kristian [Vis alle 8 forfattere av denne artikkelen] (2018). Enhancing the effects of chemotherapy by combined macrophage-mediated photothermal therapy (PTT) and photochemical internalization (PCI). Lasers in Medical Science. ISSN 0268-8921. 33(8), s. 1747–1755. doi: 10.1007/s10103-018-2534-5.
• 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, s. 35–47. doi: 10.1016/j.pdpdt.2017.08.010.
• Christie, Catherine; Pomeroy, Aftin; Nair, Rohit; Berg, Kristian & Hirschberg, Henry (2017). Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 18, s. 140–148. doi: 10.1016/j.pdpdt.2017.02.016.
• Sellevold, Simen; Qian, Peng; Fremstedal, Ane Sofie Viset & Berg, Kristian (2017). Photochemical internalization (PCI) of bleomycin is equally effective in two dissimilar leiomyosarcoma xenografts in athymic mice. Photodiagnosis and Photodynamic Therapy. ISSN 1572-1000. 20, s. 95–106. doi: 10.1016/j.pdpdt.2017.08.015.
• Norum, Ole-Jacob Anderssen; Fremstedal, Ane Sofie Viset; Weyergang, Anette; Golab, Jakub & Berg, Kristian (2017). Photochemical delivery of bleomycin induces T-cell activation of importance for curative effect and systemic anti-tumor immunity. Journal of Controlled Release. ISSN 0168-3659. 268, s. 120–127. doi: 10.1016/j.jconrel.2017.10.015.
• Gaware, Vivek S.; Håkerud, Monika; Juzeniene, Asta; Høgset, Anders; Berg, Kristian & Másson, Már (2017). Endosome Targeting meso-Tetraphenylchlorin-Chitosan Nanoconjugates for Photochemical Internalization. Biomacromolecules. ISSN 1525-7797. 18(4), s. 1108–1126. doi: 10.1021/acs.biomac.6b01670.
• 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. ISSN 2213-2317. 12, s. 191–197. doi: 10.1016/j.redox.2017.02.018.
• Olsen, Cathrine Elisabeth; Weyergang, Anette; Edwards, Victoria Tudor; Berg, Kristian; Brech, Andreas & Weisheit, Sabine [Vis alle 8 forfattere av denne artikkelen] (2017). Development of resistance to photodynamic therapy (PDT) in human breast cancer cells is photosensitizer-dependent: Possible mechanisms and approaches for overcoming PDT-resistance. Biochemical Pharmacology. ISSN 0006-2952. 144, s. 63–77. doi: 10.1016/j.bcp.2017.08.002.
• Gederaas, Odrun Arna; Johnsson, Anders Carl G.; Berg, Kristian; Manandhar, Rojlina; Shrestha, Chetana & Skåre, Daniel [Vis alle 9 forfattere av denne artikkelen] (2017). Photochemical internalization in bladder cancer-development of an orthotopic in vivo model. Photochemical and Photobiological Sciences. ISSN 1474-905X. 16(11), s. 1664–1676. doi: 10.1039/c7pp00176b.
• Berg, Kristian & Selbo, Pål Kristian (2016). Photochemical Internalization (PCI) — A Technology for Intracellular Drug Delivery. I Karl M, Kadish; Smith, Kevin M. & Guilard, Roger (Red.), Handbook of Porphyrin Science: With Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medicine. World Scientific. ISSN 978-981-3149-63-2. s. 245–300. doi: 10.1142/9789813149632_0004.
• Weyergang, Anette; Berg, Kristian & Selbo, Pål Kristian (2016). Photochemical Internalization-Enhanced Targeting of Vasculature and Cancer Stem Cells - Present and Future Perspectives. Comprehensive Series in Photochemical and Photobiological Sciences. ISSN 2041-9716. 15, s. 161–180. doi: 10.1039/9781782626824-00161.
• Sultan, Ahmed A.; Jerjes, Waseem; Berg, Kristian; Høgset, Anders; Mosse, Charles A. & Hamoudi, Rifat [Vis alle 11 forfattere av denne artikkelen] (2016). Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial. The Lancet Oncology. ISSN 1470-2045. 17(9), s. 1217–1229. doi: 10.1016/S1470-2045(16)30224-8.
• Madsen, Steen J.; Gonzales, Jonathan; Zamora, Genesis; Berg, Kristian; Nair, Rohit Kumar & Hirschberga, Henry (2016). Comparing the effects of light-or sonic-activated drug delivery: Photochemical/sonochemical internalization. Journal of Environmental Pathology And Toxicology. ISSN 0731-8898. 35(1), s. 91–98. doi: 10.1615/JEnvironPatholToxicolOncol.2016015463.
• Reichrath, Jörg; Berg, Kristian; Emmert, Steffen; Lademann, Jürgen; Seckmeyer, Gunther & Zastrow, Leonhard [Vis alle 8 forfattere av denne artikkelen] (2016). Biologic effects of light: An enlighting prospective. Anticancer Research. ISSN 0250-7005. 36(3), s. 1339–1344.
• Christie, Catherine; Molina, Stephanie; Gonzales, Jonathan; Berg, Kristian; Nair, Rohit Kumar & Huynh, Khoi [Vis alle 8 forfattere av denne artikkelen] (2016). Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization. Biomedical Optics Express. ISSN 2156-7085. 7(4), s. 1240–1250. doi: 10.1364/BOE.7.001240.
• 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), s. 251–262. doi: 10.1021/acschembio.5b00734.
• Berstad, Maria Elisabeth Brandal; Cheung, LH; Berg, Kristian; Qian, Peng; Fremstedal, Ane Sofie Viset & Patzke, Sebastian [Vis alle 8 forfattere av denne artikkelen] (2015). Design of an EGFR-targeting toxin for photochemical delivery: In vitro and in vivo selectivity and efficacy. Oncogene. ISSN 0950-9232. 34(44), s. 5582–5592. doi: 10.1038/onc.2015.15.
• Selbo, Pål Kristian; Bostad, Monica; Olsen, Cathrine; Edwards, Victoria Tudor; Høgset, Anders & Weyergang, Anette [Vis alle 7 forfattere av denne artikkelen] (2015). Photochemical internalisation, a minimally invasive strategy for light-controlled endosomal escape of cancer stem cell-targeting therapeutics. Photochemical and Photobiological Sciences. ISSN 1474-905X. 14(8), s. 1433–1450. doi: 10.1039/c5pp00027k.
• Weyergang, Anette; Berstad, Maria Elisabeth Brandal; Bull-Hansen, Bente; Olsen, Cathrine; Selbo, Pål Kristian & Berg, Kristian (2015). Photochemical activation of drugs for the treatment of therapy-resistant cancers. Photochemical and Photobiological Sciences. ISSN 1474-905X. 14(8), s. 1465–1475. doi: 10.1039/c5pp00029g.
• Bull-Hansen, Bente; Berstad, Maria Elisabeth Brandal; Berg, Kristian; Cao, Yu; Skarpen, Ellen & Fremstedal, Ane Sofie Viset [Vis alle 9 forfattere av denne artikkelen] (2015). Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer. OncoTarget. ISSN 1949-2553. 6(14), s. 12436–12451. doi: 10.18632/oncotarget.3814.
• Christie, Catherine E.; Zamora, Genesis; Kwon, Young Jik; Berg, Kristian; Madsen, Steen J. & Hirschberg, Henry (2015). Macrophage mediated PCI enhanced gene-directed enzyme prodrug therapy. Progress in Biomedical Optics and Imaging. ISSN 1605-7422. 9305. doi: 10.1117/12.2082590.
• Bostad, Monica; Olsen, Cathrine; Qian, Peng; Berg, Kristian; Høgset, Anders & Selbo, Pål Kristian (2015). Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy. Journal of Controlled Release. ISSN 0168-3659. 206, s. 37–48. doi: 10.1016/j.jconrel.2015.03.008.
• Baglo, Yan; Qian, Peng; Hagen, Lars; Berg, Kristian; Høgset, Anders & Drabløs, Finn [Vis alle 7 forfattere av denne artikkelen] (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), s. 58–66. doi: 10.1016/j.pdpdt.2014.12.005.
• Gederaas, Odrun Arna; Hauge, Anette; Ellingsen, Pål Gunnar; Berg, Kristian; Altin, Dag & Bardal, Tora [Vis alle 8 forfattere av denne artikkelen] (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), s. 1357–1366. doi: 10.1039/c5pp00144g.
• Berg, Kristian; Weyergang, Anette; Vikdal, Marie; Norum, Ole-Jacob & Selbo, Pål Kristian (2014). Photochemical Internalization: A novel Technology for Targeted Macromolecule Therapy. I Abdel-Kader, Mahmoud H. (Red.), Photodynamic Therapy - From Theory to Application. Springer. ISSN 978-3-642-39629-8. s. 119–130. doi: 10.1007/978-3-642-39629-8_6. Vis sammendrag

  Photodynamic Therapy: From Theory to Application brings attention to an exceptional treatment strategy, which until now has not achieved the recognition and breadth of applications it deserves. The authors, all experts and pioneers in their field, discuss the history and basic principles of PDT, as well as the fundamentals of the theory, methods, and instrumentation of clinical diagnosis and treatment of cancer. Non-oncological applications such as the use of PDT in control of parasites and noxious insects are also discussed. This book serves as a standard reference for researchers and students at all levels, clinical specialists interested in the topic and those in industry exploring new areas for development. A comprehensive exposition of both the theory and application of PDT, this book fills the gaps in the current literature by bringing together both basic understanding of the process of PDT and an expanded vision of its applications.

• Wang, Frederick; Zamora, Genesis; Sun, Chung-Ho; Trinidad, Anthony; Berg, Kristian & Madsen, Steen [Vis alle 8 forfattere av denne artikkelen] (2014). Photochemical internalization (PCI) enhanced nonviral transfection of tumor suppressor and pro-drug activating genes; A potential treatment modality for gliomas. Progress in Biomedical Optics and Imaging. ISSN 1605-7422. 8928:8928OB. doi: 10.1117/12.2041627.
• Sobczynski, Jan; Kristensen, Solveig & Berg, Alf Kristian (2014). The influence of Pluronics nanovehicles on dark cytotoxicity, photocytotoxicity and localization of four model photosensitizers in cancer cells. Photochemical and Photobiological Sciences. ISSN 1474-905X. 13(1), s. 8–22. doi: 10.1039/c3pp50181g. Vis sammendrag

  Many photosensitizers (PSs) for use in photodynamic therapy (PDT) are characterized by poor solubility and a tendency to aggregate in aqueous environments. Nanovehicles of Pluronics block copolymers may be used for drug delivery of antineoplastic agents and may also exert a separate effect in enhancing drug efficiency. The objective of this study was to determine the effects of selected Pluronics (F127, P123, L44 and F68) on the dark cytotoxicity, photocytotoxicity and localization of four model photosensitizers, tetraphenyl porphyrins 4-substituted on the phenyl groups with trimethylamine (TAPP), hydroxyl (THPP), sulfonate (TSPP) and carboxyl (TCPP) in cancer cells. The selected PSs showed a 3 log range in sensitivity to cellular photoinactivation. Pluronics were found to efficiently deaggregate the PSs and improve PS solubility as analyzed by fluorescence spectroscopy and dynamic light scattering. The Pluronics had moderate to profound effects on intracellular localization of the PSs and cellular sensitivity to photoinactivation. Confocal microscopy was used to determine the localization of PSs in colon adenocarcinoma cell line (WiDr), guided by co-staining with nuclear (Hoechst 33342) and endolysosomal (LysoTracker Green DND® 26 and Dextran Alexa Fluor® 488) markers. Of the most significant effects P123 and F127 strongly attenuated the uptake and photocytotoxicity of THPP and redirected the cellular uptake to endocytosis. P123 stimulated translocation of TAPP from endocytic vesicles to a cytosolic and nuclear localization followed by an enhanced phototoxicity. In the absence of Pluronics TCPP was found to localize partly in endocytic vesicles and partly in the cytosol and nucleus, while P123 and F127 lowered the fraction in endocytic vesicles followed by a reduced sensitivity to photoinactivation. F68 had only moderate effects on intracellular localization of the evaluated PSs with the exception of a higher endocytic accumulation of TCPP and lowered photocytotoxicity of TCPP and THPP. In conclusion, Pluronics are attractive solubilizers of porphyrin-based PSs which have in many cases substantial effects on intracellular localization and efficacy of the PSs.

• Garaiova, Zuzana; Strand, Sabina P.; Reitan, Nina Kristine; Lelu, Sylvie; Størset, Sigmund Østtveit & Berg, Alf Kristian [Vis alle 10 forfattere av denne artikkelen] (2012). Cellular uptake of DNA-chitosan nanoparticles: The role of clathrin- and caveolae-mediated pathways. International Journal of Biological Macromolecules. ISSN 0141-8130. 51(5), s. 1043–1051. doi: 10.1016/j.ijbiomac.2012.08.016.
• Weyergang, Anette; Selbo, Pål Kristian & Berg, Alf Kristian (2012). Sustained EKR inhibition by EGFR targeting therapies is a predictive factor for synergistic cytotoxicity with PDT as neoadjuvant therapy. Biochimica et Biophysica Acta. ISSN 0006-3002. 1830(3), s. 2659–2670. doi: 10.1016/j.bbagen.2012.11.010.
• Berg, Alf Kristian; Nordstrand, Solveig; Selbo, Pål Kristian; Thuy Thi Tran, Diem; Angell-Petersen, Even & Høgset, Anders (2011). Disulfonated tetraphenyl chlorin (TPCS2a), a novel photosensitizer developed for clinical utilization of photochemical internalization. Photochemical and Photobiological Sciences. ISSN 1474-905X. 10(10), s. 1637–1651. doi: 10.1039/c1pp05128h.
• Upile, Tahwinder; Jerjes, Waseem K.; Sterenborg, Henricus J. C. M.; Wong, Brian J.; El-Naggar, Adel & Ilgner, Justus [Vis alle 40 forfattere av denne artikkelen] (2011). At the frontiers of surgery: review. Head & Neck Oncology. ISSN 1758-3284. 3. doi: 10.1186/1758-3284-3-7.
• Jerjes, Waseem K.; Upile, Tahwinder; Wong, Brian J.; Betz, Christian S.; Sterenborg, Henricus J. C. M. & Witjes, Max J. [Vis alle 39 forfattere av denne artikkelen] (2011). The future of medical diagnostics: review paper. Head & Neck Oncology. ISSN 1758-3284. 3. doi: 10.1186/1758-3284-3-38.
• Weyergang, Anette; Selbo, Pål Kristian; Berstad, Maria Elisabeth Brandal; Bostad, Monica & Berg, Alf Kristian (2011). Photochemical Internalization of Tumor-Targeted Protein Toxins. Lasers in Surgery and Medicine. ISSN 0196-8092. 43(7), s. 721–733. doi: 10.1002/lsm.21084.
• Agostinis, Patrizia; Berg, Alf Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W. & Gollnick, Sandra O. [Vis alle 17 forfattere av denne artikkelen] (2011). Photodynamic Therapy of Cancer: An Update. CA: A Cancer Journal for Clinicians. ISSN 0007-9235. 61(4), s. 250–281. doi: 10.3322/caac.20114.
• Selbo, Pål Kristian; Weyergang, Anette; Høgset, Anders; Norum, Ole-Jacob Anderssen; Berstad, Maria Elisabeth Brandal & Vikdal, Marie [Vis alle 7 forfattere av denne artikkelen] (2010). Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules. Journal of Controlled Release. ISSN 0168-3659. 148(1), s. 2–12. doi: 10.1016/j.jconrel.2010.06.008.
• Woodhams, Josephine; Lou, Pei-Jen; Selbo, Pål Kristian; Mosse, Alexander; Oukrif, Dahmane & MacRobert, Alexander [Vis alle 10 forfattere av denne artikkelen] (2010). Intracellular re-localisation by photochemical internalisation enhances the cytotoxic effect of gelonin - Quantitative studies in normal rat liver. Journal of Controlled Release. ISSN 0168-3659. 142(3), s. 347–353. doi: 10.1016/j.jconrel.2009.11.017.
• Reiners, John J.; Agostinis, Patrizia; Berg, Alf Kristian; Oleinick, Nancy L. & Kessel, David H. (2010). Assessing autophagy in the context of photodynamic therapy. Autophagy. ISSN 1554-8627. 6(1), s. 7–18. doi: 10.4161/auto.6.1.10220.
• Berg, Kristian; Weyergang, Anette; Prasmickaite, Lina; Bonsted, Anette; Høgset, Anders & Strand, Marie-Therese R. [Vis alle 8 forfattere av denne artikkelen] (2010). Photochemical Internalization (PCI): A Technology for Drug Delivery. I Gomer, Charles J. (Red.), Photodynamic Therapy - Methods and Protocols. Humana Press. ISSN 978-1-60761-697-9. s. 133–145. doi: 10.1007/978-1-60761-697-9_10. Vis sammendrag

  Biological interactions of visible light with photosensitizers have been studied for over a century while controlled clinical applications of light and photosensitizers to treat solid tumors, known as photodynamic therapy, have been evolving since the mid 1970’s. In Photodynamic Therapy: Methods and Protocols, leading PDT scientists and clinicians provide the first comprehensive collection of methods and protocols specifically related to relevant mechanistic, dosimetric, preclinical, and clinical procedures used in current PDT research. Reflecting the growing number of studies demonstrating that immunological, tumor microenvironmental, and vascular responses are all contributing to PDT treatment outcomes, the contents of this volume move beyond the more traditional PDT concepts in order to investigate the numerous signal transduction and cell death pathways involved. Written in the highly successful Methods in Molecular Biology™ series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes which highlight tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Photodynamic Therapy: Methods and Protocols is an ideal guide for new investigators just starting out in PDT research as well as seasoned investigators changing the direction of their research with the intention of exploring this vital field of study.

• Berg, Kristian; Weyergang, Anette; Høgset, Anders & Selbo, Pål Kristian (2010). The Potential of Photochemical Internalization (PCI) for the Cytosolic Delivery of Nanomedicines. I Weissig, Volkmar & D'Souza, Gerard G.M. (Red.), Organelle‐Specific Pharmaceutical Nanotechnology. John Wiley & Sons. ISSN 9780470875780. s. 311–322. doi: 10.1002/9780470875780.ch17. Vis sammendrag

  Photochemical internalization (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induces a release of macromolecules from their compartmentalization in endocytic vesicles. PCI has been shown to enhance the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus, oligonucleotides, and the chemotherapeuticum bleomycin. PCI has also been shown to enhance the treatment effect of targeted therapeutic macromolecules. The results show that PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that PCI may have a variety of useful applications for site-specific drug delivery, e.g., in gene therapy, vaccination, and cancer treatment. Our studies also indicate that PCI of bleomycin is superior to PDT in targeting the tumor periphery and that this is partly the cause of the improved treatment effect of PCI as compared to PDT.

• Mojzisova, Halina; Bonneau, Stephanie; Maillard, Philippe; Berg, Alf Kristian & Brault, Daniel (2009). Photosensitizing properties of chlorins in solution and in membrane-mimicking systems. Photochemical and Photobiological Sciences. ISSN 1474-905X. 8(6), s. 778–787. doi: 10.1039/b822269j.
• Norum, Ole-Jacob Anderssen; Gaustad, Jon-Vidar; Angell-Petersen, Even; Rofstad, Einar K; Qian, Peng & Giercksky, Karl-Erik [Vis alle 7 forfattere av denne artikkelen] (2009). Photochemical Internalization of Bleomycin is Superior to Photodynamic Therapy Due to the Therapeutic Effect in the Tumor Periphery. Photochemistry and Photobiology. ISSN 0031-8655. 85(3), s. 740–749. doi: 10.1111/j.1751-1097.2008.00477.x.
• Berg, Kristian; Bonsted, Anette; Weyergang, Anette; Høgset, Anders & Selbo, Pål Kristian (2008). Photochemical internalization. I Hamblin, Michael (Red.), Advances in Photodynamic Therapy: Basic, Translational and Clinical. Artech House. ISSN 1596932775. s. 299–312.
• Weyergang, Anette; Selbo, Pål Kristian & Berg, Kristian (2007). Y1068 phosphorylation is the most sensitive target of disulfonated tetraphenylporphyrin-based photodynamic therapy on epidermal growth factor receptor. Biochemical Pharmacology. ISSN 0006-2952. 74(2), s. 226–235. doi: 10.1016/j.bcp.2007.04.018.
• Weyergang, Anette; Selbo, Pål Kristian & Berg, Kristian (2006). Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin. Journal of Controlled Release. ISSN 0168-3659. 111(1-2), s. 165–173. doi: 10.1016/j.jconrel.2005.12.002.
• Selbo, Pål Kristian; Weyergang, Anette; Bonsted, Anette; Bown, Stephen G. & Berg, Kristian (2006). Photochemical internalization of therapeutic macromolecular agents: a novel strategy to kill multidrug resistant cancer cells. Journal of Pharmacology and Experimental Therapeutics. ISSN 0022-3565. 319(2), s. 604–612. doi: 10.1124/jpet.106.109165.
• Dietze, Andreas; Selbo, Pål Kristian; Prasmickaite, Lina; Weyergang, Anette; Bonsted, Anette & Engesæter, Birgit [Vis alle 8 forfattere av denne artikkelen] (2006). Photochemical Internalization (PCI): A New Modality for Light Activation of Endocytosed Therapeuticals. Journal of Environmental Pathology And Toxicology. ISSN 0731-8898. 25(1-2), s. 521–536. doi: 10.1615/JEnvironPatholToxicolOncol.v25.i1-2.330.
• Berg, Kristian; Høgset, Anders; Prasmickaite, Lina; Weyergang, Anette; Bonsted, Anette & Dietze, Andreas [Vis alle 11 forfattere av denne artikkelen] (2006). Photochemical internalization (PCI): A novel technology for activation of endocytosed therapeutic agents. Medical Laser Application. ISSN 1615-1615. 21(4), s. 239–250. doi: 10.1016/j.mla.2006.08.004.
• Dietze, Andreas; Peng, Qian; Selbo, Pål Kristian; Kaalhus, Olav; Müller, Christoph & Bown, Stephen [Vis alle 7 forfattere av denne artikkelen] (2005). Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin. British Journal of Cancer. ISSN 0007-0920. 92(11), s. 2004–2009. doi: 10.1038/sj.bjc.6602600.
• Berg, Kristian; Selbo, Pål Kristian; Weyergang, Anette; Dietze, Andreas; Prasmickaite, Lina & Bonsted, Anette [Vis alle 11 forfattere av denne artikkelen] (2005). Porphyrin-related photosensitizers for cancer imaging and therapeutic applications. Journal of Microscopy. ISSN 0022-2720. 218, s. 133–147. doi: 10.1111/j.1365-2818.2005.01471.x.
• Høgset, Anders; Prasmickaite, Lina; Selbo, Pål Kristian; Hellum, Marit; Engesæter, Birgit Øvstebø & Bonsted, Anette [Vis alle 7 forfattere av denne artikkelen] (2004). Photochemical internalisation in drug and gene delivery. Advanced Drug Delivery Reviews. ISSN 0169-409X. 56(1), s. 95–115. doi: 10.1016/j.addr.2003.08.016.
• Berg, Kristian; Selbo, Pål Kristian; Prasmickaite, Lina & Høgset, Anders (2004). Photochemical drug and gene delivery. Current opinion in molecular therapeutics (Print). ISSN 1464-8431. 6(3), s. 279–287. Vis sammendrag

  The utilization of macromolecules in the therapy of cancer and other diseases is becoming increasingly relevant. Recent advances in molecular biology and biotechnology have made it possible to improve the targeting and design of cytotoxic agents or DNA complexes for clinical applications. In many cases, to achieve the desired biological effect of these macromolecules, internalization to the cell cytosol is crucial. Although new delivery systems have improved the cellular uptake of macromolecules, tissue penetration, cellular uptake and efficient transfer of the molecules into the cytosol of target cells are still fundamental obstacles. At an intracellular level, the greatest obstruction for cytosolic release of the therapeutic molecule is the membrane barrier of endocytic vesicles. Photochemical activation and delivery of drugs and genes are novel technologies to overcome these obstacles. The background theory to these technologies is described in this review and recent data in this field are discussed.

• Berg, Kristian; Prasmickaite, Lina; Selbo, Pål Kristian; Hellum, Marit; Bonsted, Anette & Engesæter, Birgit Øvstebø [Vis alle 8 forfattere av denne artikkelen] (2003). Photochemical Internalisation - A novel technology for light-directed delivery of macromolecule therapy, Targeted Cancer Therapies. An Odyssey. Ravnetrykk. ISSN 82-91378-32-0. s. 168–172.
• Selbo, Pål Kristian; Høgset, Anders; Prasmickaite, Lina & Berg, Kristian (2002). Photochemical internalisation (PCI) - a novel drug delivery system. Tumour Biology. ISSN 1010-4283. 23(2). doi: 10.1159/000059713.
• Prasmickaite, Lina; Høgset, Anders; Selbo, Pål Kristian; Engesæter, Birgit Øvstebø; Hellum, Marit & Berg, Kristian (2002). Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy. British Journal of Cancer. ISSN 0007-0920. 86(4), s. 652–657. doi: 10.1038/sj.bjc.6600138.
• Selbo, Pål Kristian; Kaalhus, Olav; Sivam, Gowsala & Berg, Kristian (2001). 5-Aminolevulinic Acid–based Photochemical Internalization of the Immunotoxin MOC31-gelonin Generates Synergistic Cytotoxic Effects In Vitro. Photochemistry and Photobiology. ISSN 0031-8655. 74(2), s. 303–310. doi: 10.1562/0031-8655(2001)0740303AABPIO2.0.CO2.
• Berg, Kristian; Selbo, Pål Kristian; Prasmickaite, Lina; Tjelle, Torunn Elisabeth; Sandvig, Kirsten & Moan, Johan [Vis alle 13 forfattere av denne artikkelen] (1999). Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Research. ISSN 0008-5472. 59(6), s. 1180–1183. Fulltekst i vitenarkiv Vis sammendrag

  https://cancerres.aacrjournals.org/content/59/6/1180

• Brustad, Tor; Voss, Torhild; Selbo, Pål Kristian; Gärtner, Kåre; Holmøy, Trond & Nesland, Jahn M [Vis alle 7 forfattere av denne artikkelen] (1997). Vital Microscopy and its use to Elucidate Photodynamic Effects. Internet Journal of Science. Biological Chemistry. ISSN 1462-2149. 3. Vis sammendrag

  Vital microscopy (VM) deals with microscopic investigations of living cells and tissues. While useful samples of the former usually are easily obtainable from most types of cell cultures, sufficiently thin samples of living tissue are more demanding to attain. A transparent chamber technique is described, by which viable tissue layers of thickness down to 20 mm are generated. Some examples from the wealth of information inherent in the dynamic scenery associated with the in vivo processes are presented. This is achieved by combination of the video-based vital microscopy technique and the electronic information technology available at the present conference. The potency of this technology is demonstrated, with examples from studies related to photodynamic therapy (PDT), based on video recordings of chamber tissue as well as of cells from tissue culture. I) VM-studies of normal chamber tissues to elucidate response patterns of different types of vessels following PDT The effects were induced by light exposure of the tissue in the transparent chamber at specified times after intra-peritoneal (i.p.) or intra-venous (i.v.) injection of 25 mg kg-1 and 3.1 mg kg-1 body weight (b. w.) of tetra (4-sulfonatophenyl) porphine (TPPS4), respectively tetra (3-hydroxyphenyl) porphine (3-THPP). In both cases photochemical effects were demonstrated; in venules by showing growth of individual deposits at certain light-exposed sites in the vessel wall, until filling the entire lumen as permanent blood plugs. Alternatively the plugs are shed off and transported in the blood stream as emboli, until trapped when blocking up the blood stream in one arm of nearby vessel bifurcations downstream, in arterioles by showing a) that myriad's of emboli are formed and shed off in succession from given growth sites, and b) constriction of the vessel, which finally may give rise to permanent or transient interruption of the blood stream. II) VM-studies of location of photosensitizers in vivo This effect was demonstrated by fluorescence microscopic analysis of the i.p. injected photosensitizer TPPS2a (disulfonated tetraphenylporphine with the sulfonate groups in adjacent positions) in the viable granular normal tissue of the transparent chamber. In normal tissue, bright fluorescence from the photosensitizer was detected mainly in the microvascular network 24 hrs post administration, while the surrounding tissue was negative. A new method for quantitative analysis of photosensitizer distribution in living tissue was established, based on well founded methods for fluorescence quantification. III) PDT-effects on cells in tissue culture Two types of such effects are shown: a) The dynamics of intracellular release from lysosomes into the cytoplasm of photochemically activated disulfonated aluminium phthalocyanine with 2 sulfonate groups in adjacent positions, AlPcS2a. This effect was demonstrated by fluorescence video microscopy of NHIK 3025 cells treated with 10 mg/ml AlPcS2a for 18 hrs followed by continuos exposure to the excitation light of the microscope. b) The dynamics of PDT-induced formation and rupture of blebs on the plasma membrane. NHIK 3025 cells were treated with 5 mg/ml monosulfonated meso-tetraphenylporphine (TPPS1) for 18 hrs, followed by continuous exposure to the excitation light of the microscope. The treatment induced bleb formation on the plasma membrane, followed by release of the cellular cytoplasm into the extracellular medium. These results indicate that TPPS1 was partly located on the plasma membrane, and that the treatment killed the cells through a necrosis pathway.

• Selbo, Pål Kristian; Brustad, Tor; Voss, Torhild; Moan, Johan & Berg, Kristian (1997). In situ localization of a photosensitizer as evaluated by vital microscopy. Proceedings of SPIE, the International Society for Optical Engineering. ISSN 0277-786X. 3191, s. 25–32. doi: 10.1117/12.297802.
• Gaullier, Jean-Michel; Berg, Kristian; Peng, Qian; Anholt, Helle; Selbo, Pål Kristian & Ma, Li-Wei [Vis alle 7 forfattere av denne artikkelen] (1997). Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Research. ISSN 0008-5472. 57(8), s. 1481–1486.

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• Longva, Ane Sager; Berg, Kristian & Weyergang, Anette (2023). Corrigendum: Light-enhanced VEGF<inf>121</inf>/rGel induce immunogenic cell death and increase the antitumor activity of αCTLA4 treatment (Frontiers in Immunology, (2023), 14, (1278000), 10.3389/fimmu.2023.1278000). Frontiers in Immunology. ISSN 1664-3224. 14. doi: 10.3389/fimmu.2023.1359973.
• Olsen, Kristine Løkke; Johansen, Harald Thidemann; Nilsen, Hilde; Solberg, Rigmor & Berg, Kristian (2020). Effekt av cysteinproteasen legumain på celleviabilitet etter fotodynamisk terapi.
• Berg, Kristian (2015). Resistance mechanisms in photodynamic therapy. Photochemical and Photobiological Sciences. ISSN 1474-905X. 14(8), s. 1376–1377. doi: 10.1039/c5pp90026c.
• 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), s. 4885–4889. doi: 10.1002/anie.201500183.
• Gederaas, Odrun Arna; Berg, Kristian & Hauge, Anette (2014). Glioma rat cancer studies using PCI technology.
• Gederaas, Odrun Arna; Høgset, Anders; Berg, Kristian; Lindgren, Mikael & Siksjø, Monica (2014). Intracellular studies on rat glioma cancer cell line using novel chromophores.
• Berg, Alf Kristian; Hopper, Colin; Weyergang, Anette; Selbo, Pål Kristian & Høgset, Anders (2013). Abstract 1606: Photochemical internalization (PCI): a novel technology for site-specific drug delivery. Vis sammendrag

  The utilization of macromolecules in therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. To achieve the expected biological effect of these macromolecules in many cases internalisation to the cell cytosol is crucial. At an intracellular level, the most fundamental obstruction for cytosolic delivery of therapeutic macromolecule is the membrane-barrier of the endocytic vesicles. Photochemical internalisation (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induces rupture of the endocytic vesicles and thereby release of the macromolecules into the cytosol. PCI has been shown to enhance the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus, oligonucleotides and the chemotherapeutic agent bleomycin. For clinical utilization a novel photosensitizer has been developed and evaluated for PCI of bleomycin. Preclinical results with this combination will be presented. Furthermore, a phase I/II dose-escalating clinical trial has been finalized and results from this trial will also be presented.

• Sobczynski, Jan; Kristensen, Solveig; Smistad, Gro; Hegge, Anne Bee; Tønnesen, Hanne Hjorth & Berg, Alf Kristian (2013). The influence of Pluronic block copolymers on solubilization and photocytotoxicity of porphyrin photosensitizers.
• Bostad, Monica; Berg, Alf Kristian; Høgset, Anders & Selbo, Pål Kristian (2012). Abstract 3381: Photochemical internalization (PCI) of immunotoxins targeting cancer stem cell markers. Vis sammendrag

  The cancer stem cell (CSC) theory indicates that only a subset of the cancer cells is capable of tumor-initiation, self renewal and differentiation. CSC is also thought to be treatment resistant and responsible for recurrence. Different antigens are being used to identify CSC markers and are potential targets for CSC-based therapy. Due to the expression of the same antigens on normal stem cells it is of paramount importance that CSC-targeting cytotoxins are specifically and efficiently delivered to malignant tissues. Photochemical internalization (PCI) is a method for specific delivery of membrane impermeable macromolecules from endocytic vesicles to the cytosol of targeted cells. In this study we show that PCI increase the cytotoxic effect of immunotoxins (IT) targeting stem cell markers on different cell lines. The IT consists of a CSC-targeting mAb biotinylated to the ribosome inactivating plant (RIP) toxin saporin. TPCS2a-PCI of one of the ITs showed to be very cytotoxic at sub picomolar levels. Cytotoxicity of the IT was blocked by using excess concentration of unconjugated Ab. In addition, no difference in cytotoxicity was obtained between mAb-toxin and toxin alone in marker negative cell lines, confirming specificity. In order to asses enrichment of CSC-activity in vitro we used flow cytometry to sort cells based on the degree of expression of CSC-markers and compared the ability of different cell fractions to establish colonies in both 2D and 3D cell cultures growing in serum-free stem cell media. Cells with high expression of CSC-markers had significantly higher capacity to initiate colonies than low expressing cells. CSC enrichment was confirmed by an in vivo limiting dilution assay. The present study demonstrates that PCI is an efficient method for selective killing of cancer cells expressing stem cell markers and will be further explored for the targeting of tumors that express these markers.

• Berg, Alf Kristian; Golab, Jakub; Korbelik, Mladen & Russell, David (2011). Drug delivery technologies and immunological aspects of photodynamic therapy. Photochemical and Photobiological Sciences. ISSN 1474-905X. 10(5), s. 647–648. doi: 10.1039/c1pp90010b.
• Selbo, Pål Kristian; Cheung, Lawrence H.; Zhang, Wendy; Rosenblum, Michael G. & Berg, Alf Kristian (2007). Photochemical internalization (PCI) of the recombinant melanoma-targeting immunotoxin scFvMEL/rGel causes rapid tumor regression in vivo. Vis sammendrag

  Intracellular sequestration of therapeutic agents and the subsequent degradation in endocytic vesicles is a major obstacle for several drug-based therapies of cancer. The purpose of the present study was to establish in vivo photochemical internalization (PCI) of a tumor-targeting immunotoxin (IT) for enhanced tumor selectivity, cytosolic delivery and anti-tumor activity. PCI is based on photodynamic therapy (PDT), a photochemical method generating reactive oxygen species (ROS) after light activation of a photosensitizer.1 The main PDT-induced ROS product is singlet oxygen, which can destroy a number of biomolecules including membrane lipids and proteins of endosomes and lysosomes.The anti-gp240 antibody fusion toxin scFvMEL/rGel2 containing the powerful ribosome-inactivating plant toxin(rGel) was tested against human non-pigmented melanoma (A-375, antigen positive) and gp-240 negative bladder carcinoma T-24 cells in vitro, and in a xenograft with A-375 injected s.c. PCI in vitro was performed by light activation of cells co-incubated with scFvMEL/rGel and the endo-lysosomal targeting photosensitizers AlPcS2a or TPPS2a. Cells were chased in drug-free medium 4 h prior to light exposure. Cytotoxicity was evaluated by the MTT assay 48 h post light. Mice with 50-100 mm3 A375 tumors got one i.p. injection of 5 mg/kg AlPcS2a 48 hrs and 2 mg/kg scFvMEL/rGel administered once i.v. 24 h prior to 670 nm laser light exposure. Fluence rate of light was 100 mW/cm2 and the total fluency given was 20 J/cm2. Tumor growth was measured twice per week until tumors reached 1000 mm3. PCI of scFvMEL/rGel demonstrated synergistic cytotoxic effects in A-375 cells in vitro, while PCI of the non-conjugated rGel was 20-fold less toxic (IC50) than the IT. There were no differences in toxicity between the IT and the toxin in gp-240 negative T-24 cells. Preliminary results in vivo show that 2 of 3 mice demonstrated a complete response after PCI of MEL scFv-rGel on day 1, while no mice receiving either light exposure of tumors with IT alone (n=5) or animals that received IT treatment alone (n=5) did not acquire a CR. Light exposure of tumors with AlPcS2a alone (photodynamic therapy, PDT) resulted in 1 CR of 8 mice (day 21). This is the first in vivo demonstration of PCI of a tumor cell-targeting macromolecule based agent. PCI of immunotoxins may be a potent drug delivery strategy which warrant further pre-clinical evaluation. Research conducted, in part, by the Clayton Foundation for Research.

• Selbo, Pål Kristian; Chung, Lawrence H.; Zhang, Wendy; Rosenblum, Michael G. & Berg, Kristian (2007). Photochemical internalization (PCI) of the recombinant melanoma-targeting immunotoxin scFvMEL/rGel causes rapid tumor regression in vivo.
• Berg, Kristian; Selbo, Pål Kristian; Prasmickaite, Lina; Olsen, Vibeke M. & Høgset, Anders (2001). Photochemical internalisation: a novel technology for improving macromolecule-based therapy. Photodynamics News. 4(1), s. 2–5.

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