Skip to main content

Advertisement

Log in

Photochemical activation of drugs for the treatment of therapy-resistant cancers

  • Perspective
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Resistance to chemotherapy, molecular targeted therapy as well as radiation therapy is a major obstacle for cancer treatment. Cancer resistance may be exerted through multiple different mechanisms which may be orchestrated as observed in multidrug resistance (MDR). Cancer resistance may be intrinsic or acquired and often leaves patients without any treatment options. Strategies for alternative treatment modalities for resistant cancer are therefore highly warranted. Photochemical internalization (PCI) is a technology for cytosolic delivery of macromolecular therapeutics based on the principles of photodynamic therapy (PDT). The present report reviews the current knowledge of PCI of therapy-resistant cancers. In summary, PCI may be able to circumvent several of the major mechanisms associated with resistance towards chemotherapeutics including increased expression of drug efflux pumps, altered intracellular drug distribution and increased ROS scavenging. Current data also suggest PCI of targeted toxins as highly effective in cancers resistant to clinically available targeted therapy such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). PCI may therefore, in general, represent a future treatment option for cancers resistant to other therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. M. R. Lackner, T. R. Wilson, J. Settleman, Mechanisms of acquired resistance to targeted cancer therapies, Future Oncol., 2012, 8, 999–1014.

    Article  CAS  PubMed  Google Scholar 

  2. P. Ramos, M. Bentires-Alj, Mechanism-based cancer therapy: resistance to therapy, therapy for resistance, Oncogene, 2014, 10, 10.1038/onc.2014.314

  3. G. Housman, S. Byler, S. Heerboth, K. Lapinska, M. Longacre, N. Snyder, et al., Drug resistance in cancer: an overview, Cancers, 2014, 6, 1769–1792.

    Article  PubMed  PubMed Central  Google Scholar 

  4. C. Holohan, S. S. Van, D. B. Longley, P. G. Johnston, Cancer drug resistance: an evolving paradigm, Nat. Rev. Cancer, 2013, 13, 714–726.

    Article  CAS  PubMed  Google Scholar 

  5. T. Ozben, Mechanisms and strategies to overcome multiple drug resistance in cancer, FEBS Lett., 2006, 580, 2903–2909.

    Article  CAS  PubMed  Google Scholar 

  6. Z. H. Siddik, Cisplatin: mode of cytotoxic action and molecular basis of resistance, Oncogene, 2003, 22, 7265–7279.

    Article  CAS  PubMed  Google Scholar 

  7. K. V. Kosuri, X. Wu, L. Wang, M. A. Villalona-Calero, G. A. Otterson, An epigenetic mechanism for capecitabine resistance in mesothelioma, Biochem. Biophys. Res. Commun., 2010, 391, 1465–1470.

    Article  CAS  PubMed  Google Scholar 

  8. J. F. Apperley, Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia, Lancet Oncol., 2007, 8, 1018–1029.

    Article  CAS  PubMed  Google Scholar 

  9. P. Nagy, E. Friedlander, M. Tanner, A. I. Kapanen, K. L. Carraway, J. Isola, et al., Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line, Cancer Res., 2005, 65, 473–482.

    CAS  PubMed  Google Scholar 

  10. A. Carracedo, L. Ma, J. Teruya-Feldstein, F. Rojo, L. Salmena, A. Alimonti, et al., Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer, J. Clin. Invest., 2008, 118, 3065–3074.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Y. Pommier, O. Sordet, S. Antony, R. L. Hayward, K. W. Kohn, Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks, Oncogene, 2004, 23, 2934–2949.

    Article  CAS  PubMed  Google Scholar 

  12. L. Lundholm, P. Haag, D. Zong, T. Juntti, B. Mork, R. Lewensohn, et al., Resistance to DNA-damaging treatment in non-small cell lung cancer tumor-initiating cells involves reduced DNA-PK/ATM activation and diminished cell cycle arrest, Cell Death Dis., 2013, 4, e478–e486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. S. Kamesaki, H. Kamesaki, T. J. Jorgensen, A. Tanizawa, Y. Pommier, J. Cossman, bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair, Cancer Res., 1993, 53, 4251–4256.

    CAS  PubMed  Google Scholar 

  14. M. I. Walton, D. Whysong, P. M. O’Connor, D. Hockenbery, S. J. Korsmeyer, K. W. Kohn, Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis, Cancer Res., 1993, 53, 1853–1861.

    CAS  PubMed  Google Scholar 

  15. B. C. Baguley, Multiple drug resistance mechanisms in cancer, Mol. Biotechnol., 2010, 46, 308–316.

    Article  CAS  PubMed  Google Scholar 

  16. A. Marusyk, K. Polyak, Tumor heterogeneity: causes and consequences, Biochim. Biophys. Acta, 2010, 1805, 105–117.

    CAS  PubMed  Google Scholar 

  17. M. Karvela, G. V. Helgason, T. L. Holyoake, Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia, Expert Rev. Anticancer Ther., 2012, 12, 381–392.

    Article  CAS  PubMed  Google Scholar 

  18. V. Nardi, M. Azam, G. Q. Daley, Mechanisms and implications of imatinib resistance mutations in BCR-ABL, Curr. Opin. Hematol., 2004, 11, 35–43.

    Article  CAS  PubMed  Google Scholar 

  19. A. Quintas-Cardama, E. J. Jabbour, Considerations for early switch to nilotinib or dasatinib in patients with chronic myeloid leukemia with inadequate response to first-line imatinib, Leuk. Res., 2013, 37, 487–495.

    Article  CAS  PubMed  Google Scholar 

  20. G. Kibria, H. Hatakeyama, H. Harashima, Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system, Arch. Pharm. Res., 2014, 37, 4–15.

    Article  CAS  PubMed  Google Scholar 

  21. K. Berg, P. K. Selbo, L. Prasmickaite, T. E. Tjelle, K. Sandvig, J. Moan, et al., Photochemical internalization: a novel technology for delivery of macromolecules into cytosol, Cancer Res., 1999, 59, 1180–1183.

    CAS  PubMed  Google Scholar 

  22. P. K. Selbo, A. Weyergang, A. Hogset, O. J. Norum, M. B. Berstad, M. Vikdal, et al., Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules, J. Controlled Release, 2010, 148, 2–12.

    Article  CAS  Google Scholar 

  23. K. Berg, S. Nordstrand, P. K. Selbo, D. T. Tran, E. Ngell-Petersen, A. Hogset, Disulfonated tetraphenyl chlorin (TPCS2a), a novel photosensitizer developed for clinical utilization of photochemical internalization, Photochem. Photobiol. Sci., 2011, 10, 1637–1651.

    Article  CAS  PubMed  Google Scholar 

  24. P. Agostinis, K. Berg, K. A. Cengel, T. H. Foster, A. W. Girotti, S. O. Gollnick, et al., Photodynamic therapy of cancer: An update, CA-Cancer J. Clin., 2011, 61, 250–281.

    Article  PubMed  PubMed Central  Google Scholar 

  25. A. Dietze, Q. Peng, P. K. Selbo, O. Kaalhus, C. Muller, S. Bown, et al., Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin, Br. J. Cancer, 2005, 92, 2004–2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. M. B. Berstad, L. H. Cheung, K. Berg, Q. Peng, A. S. Fremstedal, S. Patzke, et al., Design of an EGFR-targeting toxin for photochemical delivery: in vitro and in vivo selectivity and efficacy, Oncogene, 2015, 10, 10.1038/onc.2015.15

  27. O. J. Norum, J. V. Gaustad, E. ngell-Petersen, E. K. Rofstad, Q. Peng, K. E. Giercksky, et al., Photochemical internalization of bleomycin is superior to photodynamic therapy due to the therapeutic effect in the tumor periphery, Photochem. Photobiol., 2009, 85, 740–749.

    Article  CAS  PubMed  Google Scholar 

  28. M. Hakerud, P. K. Selbo, Y. Waeckerle-Men, E. Contassot, P. Dziunycz, T. M. Kundig, et al., Photosensitisation facilitates cross-priming of adjuvant-free protein vaccines and stimulation of tumour-suppressing CD8 T cells, J. Controlled Release, 2015, 198, 10–17.

    Article  CAS  Google Scholar 

  29. M. Hakerud, Y. Waeckerle-Men, P. K. Selbo, T. M. Kundig, A. Hogset, P. Johansen, Intradermal photosensitisation facilitates stimulation of MHC class-I restricted CD8 T-cell responses of co-administered antigen, J. Controlled Release, 2014, 174, 143–150.

    Article  CAS  Google Scholar 

  30. K. Svanberg, N. Bendsoe, J. Axelsson, S. Andersson-Engels, S. Svanberg, Photodynamic therapy: superficial and interstitial illumination, J. Biomed. Opt., 2010, 15, 041502.

    Article  PubMed  Google Scholar 

  31. K. Berg, A. Dietze, O. Kaalhus, A. Hogset, Site-specific drug delivery by photochemical internalization enhances the antitumor effect of bleomycin, Clin. Cancer Res., 2005, 11, 8476–8485.

    Article  CAS  PubMed  Google Scholar 

  32. J. M. Vergnon, R. M. Huber, K. Moghissi, Place of cryotherapy, brachytherapy and photodynamic therapy in therapeutic bronchoscopy of lung cancers, Eur. Respir. J., 2006, 28, 200–218.

    Article  PubMed  Google Scholar 

  33. T. Yano, K. Hatogai, H. Morimoto, Y. Yoda, K. Kaneko, Photodynamic therapy for esophageal cancer, Ann. Transl. Med., 2014, 2, 29–5839.

    PubMed  PubMed Central  Google Scholar 

  34. D. Bechet, S. R. Mordon, F. Guillemin, M. A. Barberi-Heyob, Photodynamic therapy of malignant brain tumours: a complementary approach to conventional therapies, Cancer Treat Rev., 2014, 40, 229–241.

    Article  PubMed  Google Scholar 

  35. O. J. Norum, K. E. Giercksky, K. Berg, Photochemical internalization as an adjunct to marginal surgery in a human sarcoma model, Photochem. Photobiol. Sci., 2009, 8, 758–762.

    Article  CAS  PubMed  Google Scholar 

  36. D. W. Pack, A. S. Hoffman, S. Pun, P. S. Stayton, Design and development of polymers for gene delivery, Nat. Rev. Drug Discovery, 2005, 4, 581–593.

    Article  CAS  PubMed  Google Scholar 

  37. V. P. Torchilin, Recent advances with liposomes as pharmaceutical carriers, Nat. Rev. Drug Discovery, 2005, 4, 145–160.

    Article  CAS  PubMed  Google Scholar 

  38. M. Wu, Enhancement of immunotoxin activity using chemical and biological reagents, Br. J. Cancer, 1997, 75, 1347–1355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. H. Fuchs, D. Bachran, H. Panjideh, N. Schellmann, A. Weng, M. F. Melzig, et al., Saponins as tool for improved targeted tumor therapies, Curr. Drug Targets, 2009, 10, 140–151.

    Article  CAS  PubMed  Google Scholar 

  40. E. Bossu, O. Amar, R. M. Parache, D. Notter, P. Labrude, C. Vigneron, et al., Determination of the maximal tumor/normal skin ratio after HpD or m-THPC administration in hairless mouse (SKh-1) by fluorescence spectroscopy—a non-invasive method, Anticancer Drugs, 1997, 8, 67–72.

    Article  CAS  PubMed  Google Scholar 

  41. W. L. Yip, A. Weyergang, K. Berg, H. H. Tonnesen, P. K. Selbo, Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization in EGFR-positive cancer cells, Mol. Pharm., 2007, 4, 241–251.

    Article  CAS  PubMed  Google Scholar 

  42. Z. Bikadi, I. Hazai, D. Malik, K. Jemnitz, Z. Veres, P. Hari, et al., Predicting P-glycoprotein-mediated drug transport based on support vector machine and three-dimensional crystal structure of P-glycoprotein, PLoS One, 2011, 6, e25815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. K. Ueda, Y. Taguchi, M. Morishima, How does P-glycoprotein recognize its substrates?, Semin. Cancer Biol., 1997, 8, 151–159.

    Article  CAS  PubMed  Google Scholar 

  44. S. Mayor, R. E. Pagano, Pathways of clathrin-independent endocytosis, Nat. Rev. Mol. Cell Biol., 2007, 8, 603–612.

    Article  CAS  PubMed  Google Scholar 

  45. P. K. Selbo, A. Weyergang, A. Bonsted, S. G. Bown, K. Berg, Photochemical internalization of therapeutic macromolecular agents: a novel strategy to kill multidrug-resistant cancer cells, J. Pharmacol. Exp. Ther., 2006, 319, 604–612.

    Article  CAS  PubMed  Google Scholar 

  46. J. W. Jonker, M. Buitelaar, E. Wagenaar, M. A. Van Der Valk, G. L. Scheffer, R. J. Scheper, et al., The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 15649–15654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. R. W. Robey, K. Steadman, O. Polgar, S. E. Bates, ABCG2-mediated transport of photosensitizers: potential impact on photodynamic therapy, Cancer Biol. Ther., 2005, 4, 187–194.

    Article  CAS  PubMed  Google Scholar 

  48. P. Krishnamurthy, D. D. Ross, T. Nakanishi, K. Bailey-Dell, S. Zhou, K. E. Mercer, et al., The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme, J. Biol. Chem., 2004, 279, 24218–24225.

    Article  CAS  PubMed  Google Scholar 

  49. P. K. Selbo, A. Weyergang, M. S. Eng, M. Bostad, G. M. Maelandsmo, A. Hogset, et al., Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug, J. Controlled Release, 2012, 159, 197–203.

    Article  CAS  Google Scholar 

  50. C. E. Olsen, K. Berg, P. K. Selbo, A. Weyergang, Circumvention of resistance to photodynamic therapy in doxorubicin-resistant sarcoma by photochemical internalization of gelonin, Free Radic. Biol. Med., 2013, 65, 1300–1309.

    Article  CAS  PubMed  Google Scholar 

  51. A. K. Larsen, A. E. Escargueil, A. Skladanowski, Resistance mechanisms associated with altered intracellular distribution of anticancer agents, Pharmacol. Ther., 2000, 85, 217–229.

    Article  CAS  PubMed  Google Scholar 

  52. N. Altan, Y. Chen, M. Schindler, S. M. Simon, Defective acidification in human breast tumor cells and implications for chemotherapy, J. Exp. Med., 1998, 187, 1583–1598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. P. J. Lou, P. S. Lai, M. J. Shieh, A. J. Macrobert, K. Berg, S. G. Bown, Reversal of doxorubicin resistance in breast cancer cells by photochemical internalization, Int. J. Cancer, 2006, 119, 2692–2698.

    Article  CAS  PubMed  Google Scholar 

  54. C. M. Lee, I. F. Tannock, Inhibition of endosomal sequestration of basic anticancer drugs: influence on cytotoxicity and tissue penetration, Br. J. Cancer, 2006, 94, 863–869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. R. A. Kramer, J. Zakher, G. Kim, Role of the glutathione redox cycle in acquired and de novo multidrug resistance, Science, 1988, 241, 694–697.

    Article  CAS  PubMed  Google Scholar 

  56. J. Chen, Reactive Oxygen Species and Drug Resistance in Cancer Chemotherapy, Austin J. Clin. Pathol., 2014, 1, 1017–1023.

    Google Scholar 

  57. M. Diehn, R. W. Cho, N. A. Lobo, T. Kalisky, M. J. Dorie, A. N. Kulp, et al., Association of reactive oxygen species levels and radioresistance in cancer stem cells, Nature, 2009, 458, 780–783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. G. H. Rodal, S. K. Rodal, J. Moan, K. Berg, Liposome-bound Zn(ii)-phthalocyanine. Mechanisms for cellular uptake and photosensitization, J. Photochem. Photobiol., B, 1998, 45, 150–159.

    Article  CAS  Google Scholar 

  59. Y. N. Wang, H. Yamaguchi, J. M. Hsu, M. C. Hung, Nuclear trafficking of the epidermal growth factor receptor family membrane proteins, Oncogene, 2010, 29, 3997–4006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. D. J. Chen, C. S. Nirodi, The epidermal growth factor receptor: a role in repair of radiation-induced DNA damage, Clin. Cancer Res., 2007, 13, 6555–6560.

    Article  CAS  PubMed  Google Scholar 

  61. C. Li, M. Iida, E. F. Dunn, A. J. Ghia, D. L. Wheeler, Nuclear EGFR contributes to acquired resistance to cetuximab, Oncogene, 2009, 28, 3801–3813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. L. Prasmickaite, A. Hogset, P. K. Selbo, B. O. Engesaeter, M. Hellum, K. Berg, Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy, Br. J. Cancer, 2002, 86, 652–657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. E. Verri, P. Guglielmini, M. Puntoni, L. Perdelli, A. Papadia, P. Lorenzi, et al., HER2/neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Clinical study, Oncology, 2005, 68, 154–161.

    Article  CAS  PubMed  Google Scholar 

  64. B. Bull-Hansen, Y. Cao, K. Berg, E. Skarpen, M. G. Rosenblum, A. Weyergang, Photochemical activation of the recombinant HER2-targeted fusion toxin MH3-B1/rGel; Impact of HER2 expression on treatment outcome, J. Controlled Release, 2014, 182, 58–66.

    Article  CAS  Google Scholar 

  65. R. Worthylake, L. K. Opresko, H. S. Wiley, ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors, J. Biol. Chem., 1999, 274, 8865–8874.

    Article  CAS  PubMed  Google Scholar 

  66. L. DeFazio-Eli, K. Strommen, T. Dao-Pick, G. Parry, L. Goodman, J. Winslow, Quantitative assays for the measurement of HER1-HER2 heterodimerization and phosphorylation in cell lines and breast tumors: applications for diagnostics and targeted drug mechanism of action, Breast Cancer Res., 2011, 13, R44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. K. Subik, J. F. Lee, L. Baxter, T. Strzepek, D. Costello, P. Crowley, et al., The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by Immunohistochemical Analysis in Breast Cancer Cell Lines, Breast Cancer, 2010, 4, 35–41.

    PubMed  PubMed Central  Google Scholar 

  68. M. Bostad, K. Berg, A. Hogset, E. Skarpen, H. Stenmark, P. K. Selbo, Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties, J. Controlled Release, 2013, 168, 317–326.

    Article  CAS  Google Scholar 

  69. M. Bostad, M. Kausberg, A. Weyergang, C. E. Olsen, K. Berg, A. Hogset, et al., Light-Triggered, Efficient Cytosolic Release of IM7-Saporin Targeting the Putative Cancer Stem Cell Marker CD44 by Photochemical Internalization, Mol. Pharm., 2014, 11, 2764–2776.

    Article  CAS  PubMed  Google Scholar 

  70. A. Weyergang, L. H. Cheung, M. G. Rosenblum, K. A. Mohamedali, Q. Peng, J. Waltenberger, et al., Photochemical internalization augments tumor vascular cytotoxicity and specificity of VEGF121/rGel fusion toxin, J. Controlled Release, 2014, 180, 1–9.

    Article  CAS  Google Scholar 

  71. C. H. Choi, ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal, Cancer Cell Int., 2005, 5, 30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. R. B. Wang, C. L. Kuo, L. L. Lien, E. J. Lien, Structure–activity relationship: analyses of p-glycoprotein substrates and inhibitors, J. Clin. Pharm. Ther., 2003, 28, 203–228.

    Article  CAS  PubMed  Google Scholar 

  73. C. Liu, G. Zhao, J. Liu, N. Ma, P. Chivukula, L. Perelman, et al., Novel biodegradable lipid nano complex for siRNA delivery significantly improving the chemosensitivity of human colon cancer stem cells to paclitaxel, J. Controlled Release, 2009, 140, 277–283.

    Article  CAS  Google Scholar 

  74. H. Meng, M. Liong, T. Xia, Z. Li, Z. Ji, J. I. Zink, et al., Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line, ACS Nano, 2010, 4, 4539–4550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. M. Leal, P. Sapra, S. A. Hurvitz, P. Senter, A. Wahl, M. Schutten, et al., Antibody-drug conjugates: an emerging modality for the treatment of cancer, Ann. N. Y. Acad. Sci., 2014, 1321, 41–54.

    Article  CAS  PubMed  Google Scholar 

  76. A. Illes, A. Jona, Z. Miltenyi, Brentuximab vedotin for treating Hodgkin’s lymphoma: an analysis of pharmacology and clinical efficacy, Expert Opin. Drug Metab. Toxicol., 2015, 11, 451–459.

    Article  CAS  PubMed  Google Scholar 

  77. D. J. Wong, S. A. Hurvitz, Recent advances in the development of anti-HER2 antibodies and antibody-drug conjugates, Ann. Transl. Med., 2014, 2, 122–5839.

    PubMed  PubMed Central  Google Scholar 

  78. E. L. Sievers, P. D. Senter, Antibody-drug conjugates in cancer therapy, Annu. Rev. Med., 2013, 64, 15–29.

    Article  CAS  PubMed  Google Scholar 

  79. F. Stirpe, S. Olsnes, A. Pihl, Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavalin A, J. Biol. Chem., 1980, 255, 6947–6953.

    Article  CAS  PubMed  Google Scholar 

  80. L. Barbieri, M. G. Battelli, F. Stirpe, Ribosome-inactivating proteins from plants, Biochim. Biophys. Acta, 1993, 1154, 237–282.

    Article  CAS  PubMed  Google Scholar 

  81. C. M. Pirie, B. J. Hackel, M. G. Rosenblum, K. D. Wittrup, Convergent potency of internalized gelonin immunotoxins across varied cell lines, antigens, and targeting moieties, J. Biol. Chem., 2011, 286, 4165–4172.

    Article  CAS  PubMed  Google Scholar 

  82. P. K. Selbo, M. Bostad, C. E. Olsen, V. T. Edwards, A. Høgset, A. Weyergang, K. Berg, Photochemical internalisation, a minimally invasive strategy for light-controlled endosomal escape of cancer stem cell-targeting therapeutics, Photochem. Photobiol. Sci., 2015

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anette Weyergang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weyergang, A., Berstad, M.E.B., Bull-Hansen, B. et al. Photochemical activation of drugs for the treatment of therapy-resistant cancers. Photochem Photobiol Sci 14, 1465–1475 (2015). https://doi.org/10.1039/c5pp00029g

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c5pp00029g

Navigation