title: Morniga G: a plant lectin as an endocytic ligand for photosensitizer molecule targeting toward tumor-associated T/Tn antigens.
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.
authors.affiliation: INSERM U858 I2MR, Institut Louis Bugnard, Toulouse, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Poiroux
authors.forename: Marguerite
authors.initials: M
authors.lastname: Pitié
authors.forename: Raphaël
authors.initials: R
authors.lastname: Culerrier
authors.forename: Bruno
authors.initials: B
authors.lastname: Ségui
authors.forename: Els J M
authors.initials: EJ
authors.lastname: Van Damme
authors.forename: Willy J
authors.initials: WJ
authors.lastname: Peumans
authors.forename: Jean
authors.initials: J
authors.lastname: Bernadou
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.forename: Pierre
authors.initials: P
authors.lastname: Rougé
authors.forename: Annick
authors.initials: A
authors.lastname: Barre
authors.forename: Hervé
authors.initials: H
authors.lastname: Benoist
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D045744:Cell Line, Tumor; D002474:Cell-Free System; D016503:Drug Delivery Systems; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy*; D017319:Photosensitizing Agents / Q000737:chemistry*; D037121:Plant Lectins / Q000737:chemistry*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D008024:Ligands; D017319:Photosensitizing Agents; D037121:Plant Lectins; C040286:Tn antigen