title: Tumor targeting in photodynamic therapy. From glycoconjugated photosensitizers to glycodendrimeric one. Concept, design and properties.
abstract: In this paper, we discuss the evolution over the last 15 years in the Curie Institute of the concept, the development of the design and some properties of glycoconjugated photosensitizers with the aim to optimize the tumor targeting in photodynamic therapy. By this research, we have shown that specific interactions between a mannose-lectin and trimannosylglycodendrimeric porphyrins contributed to a larger extent than non-specific ones to the overall interaction of a glycosylated tetraarylporphyrin with a membrane. The studies of in vitro photocytotoxicity showed the relevance of the global geometry of the photosensitizer, the number and position of the linked glycopyranosyl groups on the chromophore and their lipophilicity. The two best compounds appeared to be porphyrins bearing three α-glycosyl groups on para-position of meso-phenyl via a flexible linker. Compound bearing α-manosyl moieties was evaluated successfully in two in vivo xenografted animal models of human retinoblastoma and colorectal cancers. Conversely, the presence on the chromophore of three sugars via a glycodendrimeric moiety induced a potential cluster effect, but decreased the in vitro photoefficiency despite a good affinity for a mannose-lectin.
authors.affiliation: Institut Curie, Centre de Recherche, Bât 110-112, Orsay, F-91405, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Ballut
authors.forename: Ali
authors.initials: A
authors.lastname: Makky
authors.forename: Benoît
authors.initials: B
authors.lastname: Chauvin
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Michel
authors.forename: Athena
authors.initials: A
authors.lastname: Kasselouri
authors.forename: Philippe
authors.initials: P
authors.lastname: Maillard
authors.forename: Véronique
authors.initials: V
authors.lastname: Rosilio
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis* / Q000494:pharmacology; D006001:Glycoconjugates / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000473:pathology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D050091:Dendrimers; D006001:Glycoconjugates; D017319:Photosensitizing Agents