Vendredi 24 septembre 2010 à 11 h 00 – À l’invitation de Chantal Pichon

«Functionalised nanoparticles for two-photon fluorescence or photodynamitherapy
»

Docteur Jean-Olivier Durand

ICGM UMR CNRS 5253 – Université Montpellier
2, Pl. E. Bataillon – 34095 Montpellier cedex 05

The use of nanotechnologies for therapeutic or diagnostic purposes to fight cancer increased considerably over the last few years. In this work, we prepared functionalised mesoporous silica nanoparticles encapsulating new two-photon chromophores in order to develop original biological markers. The template-directed synthesis of mesoporous silica nanoparticles doped with water-soluble fluorescent dyes optimized for two-photon excitation is described. Two structurally related symmetrical two-photon dyes that possess pyridinium acceptor end-groups conjugated to a fluorenyl core were synthesized by Heck coupling. These dyes display bright fluorescence (Φ ≈ 0.35) under both one- (ε ≈ 6 x 104 M-1 cm-1) and two-photon excitation (σ2 ≈ 1000 GM) and were successfully encapsulated in silica nanoparticles via immobilization through non-covalent interactions. The nanoparticles presented a mean diameter of 100 nm and a hexagonal network of mesopores. Interestingly the photophysical characteristics of the dyes are retained upon their immobilization into the silica matrix, leading to fluorescent silica nanoparticles with unprecedented TPA cross-section (107 GM). The two-photon dye-doped mesoporous silica nanoparticles were conjugated with folic acid for bioimaging of cancer cells. Cytotoxicity studies performed with MCF7 and HeLa cancer cells demonstrated that these functionalized NPs are much less cytotoxic than the non-functionalized NPs against both cell lines. Such nanospheres represent attractive nanoplatforms for the development of biotargeted biocompatible luminescent tracers.

Alternatively, covalent attachment of water-soluble photosensitizers (Figure 1) into mesoporous silica nanoparticles (MSN) for photodynamic therapy (PDT) applications is described. Those MSN were monodisperse with a diameter of 100 nm, a specific surface area of 860 m2/g and a pores diameter of 2.2 nm. These MSN were proved to be active on breast cancer cells after endocytosis. Moreover, MSN were functionalized on their surface by mannose using an original pathway with diethyl squarate as the linker. Those mannose-functionalized MSN dramatically improved the efficiency of PDT on breast cancer cells. In addition, the involvement of mannose receptors for the active endocytosis of mannose-functionalized MSN was demonstrated (Figure 2).