Morniga G: A Plant Lectin as an Endocytic Ligand for Photosensitizer Molecule Targeting Toward Tumor-Associated T/Tn Antigens

• Published in: Photochemistry and photobiology 2011-03, Vol.87 (2), p.370-377
• Main Authors: Poiroux, Guillaume, Pitié, Marguerite, Culerrier, Raphaël, Ségui, Bruno, Van Damme, Els J.M., Peumans, Willy J., Bernadou, Jean, Levade, Thierry, Rougé, Pierre, Barre, Annick, Benoist, Hervé
• Format: Article
• Language: English
• Subjects: Antigens, Tumor-Associated, Carbohydrate - chemistry; Apoptosis; Cancer; Cell Line, Tumor; Cell-Free System; Cytotoxicity; Drug Delivery Systems; Humans; Irradiation; Jurkat Cells; Leukemia; Ligands; Lymphocytes; Mass spectrometry; Microscopic analysis; Neoplasms - drug therapy; Photodynamic therapy; Photosensitizing Agents - chemistry; Phototoxicity; Plant Lectins - chemistry; Proteins; Sabatier, Paul (1854-1941); Spectrum analysis; Studies; Sugar; Tumors
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/j.1751-1097.2010.00858.x

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.