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Team description

Porphyrin Chemistry

par Philippe Maillard - 20 février 2009

Chemistry of porphyrins, applications in dynamic phototherapy (PDT) UMR 176 CNRS-Institut Curie "Conception, synthèse et vectorisation de biomolécules", Bâtiments 110-112, centre universitaire, 91405 Orsay. Ph. Maillard (DR2 CNRS), E-mail : Tél : 33 (0)1 69 86 31 71, Fax 33 (0)1 69 07 53 27. S. Ballut (PhD), S. Achelle (post doct position), G. Garcia (post doc position).

This theme is in direct drive with the objectives of the Institut Curie concerning the improvement of the treatments of paediatric cancers in pecular retinoblastoma. The accent is put on the cellular targeting either by glycoconjugated porphyrins recognizing specific membrane lectines, or by targeting via a toxin (Retrograde Delivery of Photosensitizer (TPPp-O-β-GluOH)3 Selectively Potentiates its Photodynamic Activity. M. Amessou et al Bioconjugate Chemistry 19, 532-538, 2008). We shall note that glycoconjugated porphyrins are excellent candidates presenting performances superior to the photosensitizing at present in hospital (foscan®). Very recent results obtained in the center of Orsay show that it is possible to estimate the effect of a glycoconjuguated photosensitizing, real-time, on xenografted mice with retinoblastoma cells, by magnetic resonance imaging of the sodium.

Three approaches are developed aiming at the optimization of the photophysical and pharmacological properties of various families of porphyrins :

- Nanoparticles, ANR PNANO "Glyconanovectors"

The optimization of mesoporous nanoparticles of silica, by a better incorporation of PS, by a derivatisation of the surface of the nanoparticle by the polyethylene glycol and motives for recognition (sugars) is in progress. The in vitro photocytotoxic efficiency of one of these systems through mannose-dependent endocytosis, was demonstrated. Experiments of in vivo antitumoral photoefficiency are envisaged. (Mannose-targeted Mesoporous Silica Nanoparticles for Photodynamic Therapy. D. Brevet, et al Chem. Commun. in presse, DOI : 10.1039/B900427K).

The synthesis and the use of these nanoparticles loaded with paramagnetic porphyrins (complexes of manganese) as agent of contrast for the MRI are in progress.

- Glycodendrimeric photosensitizers A strategy of optimization of the biological properties of a glycoconjuguated molecule is to use the efficiency of recognition of glycodendrimeric moieties towards specific membrane lectines. A study of the chemical variety of glycodendrimeric porphyrin family is systematically made, the in vitro phototoxicity being estimated for all new compound on various cancer cell lines and in pecular on retinoblastoma. The best candidate will be tested in vivo on the animal model of retinoblastoma, the tumor evolution being followed by Na MRI and histology.

Fig 1 Example of structure of glycodendrimeric porphyrins

This glycodendrimeric PS is estimated qualitatively and quantitatively as unit recognized by specific membrane receptors on a model of biological membrane (monolayer or liposome incorporating lectines). (New strategy for targeting of photosensitizers. Synthesis of glycodendrimeric phenylporphyrins, incorporation into a liposome membrane and interaction with a specific lectin. S. Ballut, et al Chem. Commun. 224-226, 2009).

- Two-photons absorption, new PS

One of the major limitations of the PDT is the weak penetration of the light in alive tissues. The absorption of two photons allows a better penetration of the beam of light and could be a solution to increase the in vivo efficiency of the photosensitizer. This domain is in height prospecting and rare biphotinic photosensitizers are published at present. In internal collaboration, new targeted biphotonic multiporphyrins, iare developed.

Bioconjugate Chemistry 19, 532-538, 2008 - 348.8 ko

Chem. Commun. 224-226, 2009 - 568.7 ko

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