Abstract
Nowadays, the increase of the number of low-size cancers in the world has prompted the development of novel multifunctional nanomaterials applied to new non-invasive therapies. These new therapies are expected to selectively eradicate the tumor, decreasing or suppressing the side effects induced in healthy tissues by current treatments. This study describes the elaboration of nanomaterials for the diagnostic and the therapy of low size cancers through a novel therapy: photodynamic therapy (PDT). This new technique involves the activation of a photosensitizer molecule (PS) with specific wavelengths of light giving rise to energy transfer cascades that yield cytotoxic reactive oxygen species leading to apoptotic and necrotic cell death.First, the elaboration of mesoporous silica nanoparticles (MSN) containing a porphyrin photosensitizer are presented for the treatment in vitro of prostate cancer and retinoblastoma through one-photon therapy. Functionalized nanoparticles with new ligands were synthesized to target the nanoparticles to prostate cancer cells. The decrease of the nanoparticle size to 20 nm was elaborated to cross the blood-retinal barrier and treat retinoblastomas.On the other hand, two new types of nanomaterials were designed for two-photon nanomedicine which leads to a deeper penetration in tissues. Bridged silsesquioxane (BS) and periodic mesoporous organosilica (PMOs) nanoparticles were designed from different types of tetra or octasilylated-photosensitizers and bis-organoalkoxysilanes such as ethane, ethylene or disulphide. Pure PS bridged silsesquioxane nanoparticles lead to efficient two-photon imaging and photodynamic therapy which were demonstrated in vitro. Disulfide-based BS nanoparticles were designed as biodegradable nanomaterials.Finally, in addition to the imaging and therapy, PMOs nanoparticles were tested in vitro as nanocarriers for drug delivery due to their mesoporosity. Gemcitabine or doxorubicin were encapsulated into the pores leading to high drug loadings. Beside the classical photosensitizers, nanodiamonds core-shells PMOs were tested as PDT agent. In addition, pure porphyrin nanoPMOs are presented for gene delivery in vitro and in vivo in a zebrafish model.