CONTEXT

Molecular two-photon absorption (TPA) has gained increasing attention over recent years, in relation with the wide-ranging applications it offers, such as photodynamic therapy (PDT). TPA also offers a number of advantages for biological or biomedical applications, including the ability for highly selective excitation in biological media, intrinsic three-dimensional resolution, and reduction of photodamage by using lower excitation intensities. Photodynamic therapy relies on photosensitizer. Photosensitizers specifically locate in malignant tissues, and transmit their energy to the excess of molecular oxygen in their surrounding, when they are excited by a light source of suitable wavelength in the visible or near infra-red spectrum. The activation of the photosensitizer generates reactive oxygen species such as free radicals and singlet oxygen. These reactive oxygen species, and particularly singlet oxygen, are toxic for the cells that surround them, and lead to the destruction of the malignant tissue in their close vicinity. These reactive oxygen species oxidise the cell membranes and lead to irreversible damages of the cells containing the photosensitizer. Photodynamic therapy is based on a two-fold selectivity: the selective irradiation of the tissues containing the photosensitizer; and the selectivity of the photosensitizer for the targeted tissues. The preparation of photosensitizer in silica nanoparticles, is acknowledged as a promising way for photodynamic therapy, but these preparations often lead to early leakage of the photosensitizer in the organism before the photosensitizer reaches the targeted cancerous cells. The present invention is about biphotonic photosensitizer avoiding this effect.

TECHNICAL DESCRIPTION

The present invention relates to biphotonic photosensitizers, silica nanoparticles containing at least one of said biphotonic photosensitizers, and their use as drugs. The invention aims first at combining both fluorescence and singlet oxygen generation in the same biphotonic photosensitizer (i.e. significant fluorescence and singlet oxygen quantum yields) for biomedical applications: targeting, monitoring (fluorescence imaging) and therapy (photosensitized production of singlet oxygen for PDT); second at avoiding leakage of the photosensitizer out of the nanoparticle to keep the full potency of the photosensitizer until irradiation of the cancerous cells. The inventors demonstrated the specificity of the photodynamic therapy with the particles according to the present invention. Then, they showed highly efficient cellular death induced by photodynamic treatment with these particles. Cytotoxicity over retinoblastoma cells Y-79 was observed and small tumors react strongly to photodynamic therapy with these nanoparticles.

BENEFITS

The invention provides silica nanoparticles functionalized by biphotonic photosensitizers without loss of biphotonic absorption properties. These particles of the invention

• Are able to target specific cells.

• Avoid the monophotonic excitation of said photosensitizers.

INDUSTRIAL APPLICATIONS

The invention could be used for non-invasive cancer treatment. For instance, photodynamic treatment with the particles of the invention could treat breast cancer, prostate cancer and retinoblastoma.

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