Abstract
We report the use of Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) as versatile nano-objects for imaging, photodynamic therapy (PDT), drug delivery and efficient adsorption and delivery of siRNA into breast cancer cells. Mesoporous ionosilica nanoparticles are well known for several advantages: high specific area and uniformity of both size and shape of pores. In order to confer to these nanoparticles PDT and siRNA photochemical internalization (PCI) properties, a porphyrin derivative was integrated into the ionosilica framework.For this purpose, we synthetized PMINPs via hydrolysis - polycondensation procedures, starting from oligosilylated ammonium and porphyrin precursors. The formation of these nano-objects was attested by transmission electron microscopy. The formed nanoparticles were then thoroughly characterized via solid state NMR, nitrogen sorption and dynamic light scattering. The spectral properties of these nanoparticles were also studied using UV-vis and fluorescence spectroscopy, attesting the successful incorporation of the porphyrin derivative.Our results indicate the formation of highly porous nanorods. A significant PDT effect was observed for both one-photon and two-photon excitation PDT, due to an important ROS production upon light irradiation in nanoparticles treated-breast cancer cells. Zeta potential measurements of PMINPs revealed the presence of positive surface charges which promoted the adsorption of siRNA and BODIPY molecules. The electrostatic complexation of siRNA was then verified by electrophoresis gel retardation assay. Furthermore, PMINPs formed stable complexes with siRNA (up to 24 hours) and were efficiently internalized into the cells after 4 hours incubation mostly with energy-dependent endocytosis process. The PCI effect was obvious under light irradiation and successfully led to luciferase gene silencing in luciferase-expressing breast cancer cells, while no gene silencing effect was observed in the absence of light. The dual effect of gene silencing by siRNA and PDT was also studied and revealed the existence of a synergistic effect.This work highlights the potential of porphyrin-doped ionosilica nanoparticles as multifunctional drug nanocarriers for nucleic acids, such as siRNA, with a triple ability to perform imaging, PDT and PCI.