In vitro photophysical and photobiological properties of Ce6-based dendrimer nanoparticles.
Résumé
Context: The photosensitizers vectorization enables better tumor localization and therefore a better tumoricidal PDT efficacy. Dendrimers are hyperbranched macromolecules that are considered as an attractive class of biocompatible nanovectors for drug targeting in tissues. In this study we report a novel PDT drug-carrier system, composed of chlorin e6 grafted to the periphery groups of poly(amido amine) dendrimers (PAMAM). Materials & Methods: The size and zeta potential of our nanoparticles were determined by dynamic light scattering (DLS). The nanoparticle singlet oxygen generation in pharynx carcinoma (FaDu) cells was assessed by luminescence at 1268 nm. Phototoxicity was evaluated by MTT assay. Uptake was assessed by chemical extraction associated with fluorescence spectroscopy measurements. Finally, the uptake mechanism was determined by the use of endocytosis specific inhibitors. Results: Ce6-dendrimers nanoparticles displayed a 40 times greater uptake along with a 25 fold higher photocytotoxic activity in FaDu cells compared to free Ce6. Also, a much longer singlet oxygen lifetime was demonstrated for Ce6-dendrimers compared to Ce6. Cellular incorporation of nanoparticles was completely inhibited at 4°C, demonstrating that uptake was mediated via endocytosis. Further investigations using specific inhibitors revealed that incorporation was partially mediated by macropinocytosis pathway. Conclusion: Dendrimeric based nanoparticles showed a good photodynamic efficacy towards cancer cells in vitro, suggesting them as a promising vehicle for PDT. In the future we shall test dendrimer-based nanoparticles in vivo, in pre-clinical models.
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