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Morniga G: a plant lectin as an endocytic ligand for photosensitizer molecule targeting toward tumor-associated T/Tn antigens

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Center for nano- and biophotonics (NB-Photonics)
Abstract
Porphyrins are used as photosensitizer (PS) in photodynamic therapy in cancer treatment. Nevertheless, the development of photochemotherapy in oncology remains limited, because of the low selectivity of PSs. In order to allow PS targeting toward tumor-associated antigens, for the first time a white-light activatable porphyrin, [5-(4-(5-carboxy-1-butoxy)-phenyl)-10,15,20-tris(4-N-methyl)-pyridiniumyl)-porphyrin] (TrMPyP) was covalently linked to Morniga G (MorG), a galactose-specific binding plant lectin, known to recognize with high-affinity tumor-associated T/Tn antigen in cell-free systems. Firstly, using fluorescein-labeled MorG, the sugar-dependent binding and uptake of lectin by Tn-positive (Jurkat lymphoid leukemia) cells was demonstrated. Secondly, the TrMPyP-MorG conjugate was molecularly characterized. Cytometric and confocal microscopic analysis demonstrated that PS covalent linking to MorG preserved sugar-dependent specific binding and uptake of lectin by Jurkat leukemia lymphocytes. Thirdly, the conjugate (with a 1:1 PS:lectin ratio) that was bound and quickly (5 min) taken-up, induced greater than 90% cytotoxicity upon irradiation at 10 nm concentration, whereas the free PS was absolutely nontoxic. On the contrary, normal lymphocytes strongly resisted to the conjugate-mediated phototoxicity. Thus, owing to their binding and endocytosis capacities, plant lectins represent promising molecules for targeting of tumor glycan alteration and to enhance the efficiency of specific delivery of PSs to tumor cells.
Keywords
CELLS, SIALOSYL-TN, PEANUT ALLERGY, LEGUME LECTINS, CONCANAVALIN-A, HUMAN-COLON-CANCER, PHOTODYNAMIC THERAPY, PORPHYRINS, BINDING, AGGLUTININ

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Citation

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Chicago
Poiroux, Guillaume, Marguerite Pitie, Raphael Culerrier, Bruno Segui, Els Van Damme, Willy J Peumans, Jean Bernadou, et al. 2011. “Morniga G: a Plant Lectin as an Endocytic Ligand for Photosensitizer Molecule Targeting Toward Tumor-associated T/Tn Antigens.” Photochemistry and Photobiology 87 (2): 370–377.
APA
Poiroux, G., Pitie, M., Culerrier, R., Segui, B., Van Damme, E., Peumans, W. J., Bernadou, J., et al. (2011). Morniga G: a plant lectin as an endocytic ligand for photosensitizer molecule targeting toward tumor-associated T/Tn antigens. PHOTOCHEMISTRY AND PHOTOBIOLOGY, 87(2), 370–377.
Vancouver
1.
Poiroux G, Pitie M, Culerrier R, Segui B, Van Damme E, Peumans WJ, et al. Morniga G: a plant lectin as an endocytic ligand for photosensitizer molecule targeting toward tumor-associated T/Tn antigens. PHOTOCHEMISTRY AND PHOTOBIOLOGY. 2011;87(2):370–7.
MLA
Poiroux, Guillaume, Marguerite Pitie, Raphael Culerrier, et al. “Morniga G: a Plant Lectin as an Endocytic Ligand for Photosensitizer Molecule Targeting Toward Tumor-associated T/Tn Antigens.” PHOTOCHEMISTRY AND PHOTOBIOLOGY 87.2 (2011): 370–377. Print.
@article{1233987,
  abstract     = {Porphyrins are used as photosensitizer (PS) in photodynamic therapy in cancer treatment. Nevertheless, the development of photochemotherapy in oncology remains limited, because of the low selectivity of PSs. In order to allow PS targeting toward tumor-associated antigens, for the first time a white-light activatable porphyrin, [5-(4-(5-carboxy-1-butoxy)-phenyl)-10,15,20-tris(4-N-methyl)-pyridiniumyl)-porphyrin] (TrMPyP) was covalently linked to Morniga G (MorG), a galactose-specific binding plant lectin, known to recognize with high-affinity tumor-associated T/Tn antigen in cell-free systems. Firstly, using fluorescein-labeled MorG, the sugar-dependent binding and uptake of lectin by Tn-positive (Jurkat lymphoid leukemia) cells was demonstrated. Secondly, the TrMPyP-MorG conjugate was molecularly characterized. Cytometric and confocal microscopic analysis demonstrated that PS covalent linking to MorG preserved sugar-dependent specific binding and uptake of lectin by Jurkat leukemia lymphocytes. Thirdly, the conjugate (with a 1:1 PS:lectin ratio) that was bound and quickly (5 min) taken-up, induced greater than 90\% cytotoxicity upon irradiation at 10 nm concentration, whereas the free PS was absolutely nontoxic. On the contrary, normal lymphocytes strongly resisted to the conjugate-mediated phototoxicity. Thus, owing to their binding and endocytosis capacities, plant lectins represent promising molecules for targeting of tumor glycan alteration and to enhance the efficiency of specific delivery of PSs to tumor cells.},
  author       = {Poiroux, Guillaume and Pitie, Marguerite and Culerrier, Raphael and Segui, Bruno and Van Damme, Els and Peumans, Willy J and Bernadou, Jean and Levade, Thierry and Rouge, Pierre and Barre, Annick and Benoist, Herve},
  issn         = {0031-8655},
  journal      = {PHOTOCHEMISTRY AND PHOTOBIOLOGY},
  keyword      = {CELLS,SIALOSYL-TN,PEANUT ALLERGY,LEGUME LECTINS,CONCANAVALIN-A,HUMAN-COLON-CANCER,PHOTODYNAMIC THERAPY,PORPHYRINS,BINDING,AGGLUTININ},
  language     = {eng},
  number       = {2},
  pages        = {370--377},
  title        = {Morniga G: a plant lectin as an endocytic ligand for photosensitizer molecule targeting toward tumor-associated T/Tn antigens},
  url          = {http://dx.doi.org/10.1111/j.1751-1097.2010.00858.x},
  volume       = {87},
  year         = {2011},
}

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