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.