Final Report Summary - MAGIC ((Nano)-Materials for cell Growth, Imaging and Communication) MaGIC deals with the synthesis, characterization, functionalization and use of porous silica-based nanoparticles for biomedical applications. The project aims to use the nanomaterials as platform for creating new drug delivery and imaging systems but also to employ them as platform to create structured surfaces for cell growth and studies in 2D and eventually in 3D models. The porous materials employed are aluminosilicate, zeolites L, crystalline nanocontainers, characterized by unidimensional channels that can be filled with small molecules that can then be released in different conditions. The surface of the nanocontainers can be functionalized in order to make the inorganic system more biocompatible and to study the effect of the different functionalization in the adsorption of proteins or other biomolecules in physiological conditions. The shape and surface functionalization can also be optimized to transport biomolecules through different biological barriers. In order to have pores larger than those of zeolites L (0.71 nm), we have also prepared and functionalized porous silica and demonstrated that it is possible to deliver oligonucleotides or peptide nucleic acids and drugs inside cancer cells. The release of the different components was investigated in details by fluorescence microscopy. The synergic effect exerts by the nucleic acid and the drug demonstrated that it is possible to have an efficient tool to fight the aggressive glioblastoma. The nanocontainers however are not biodegradable and they remain in the cells preventing their possible use in vivo. To overcome this drawback, very recently we succeed to synthesize a breakable silica framework. The strategy is based on the introduction in the silica network of organic moieties that are broken, by an external stimulus to form other molecules and, as a consequence, a breaking of the organo-silica is realized. We have developed porous particles as well as breakable capsules, the latter able to encapsulate biomolecules. Such innovative technology allows not only the delivery of drugs but also the release on demand of active proteins. The possibility to trigger the liberation of biomolecules opens interesting challenges towards the cure of different diseases. Besides the use of such nanocontainers as carriers and drug delivery we have shown that their arrangement in monolayers can lead to the patterning of surface and their functionalization to the formation of bio-carpet on which cells can grow and proliferate. The possibility to print different molecules on top of the nanopatterned systems resulted in a selective adhesion of certain type of cells. Such finding can be explored in the future development of diagnostics sensors or as a platform for the capture/separation of desired cells. We have also demonstrated that for disc-shaped particles it is possible to functionalize the two side with orthogonal groups or even with nano-objects. To translate the concept of cell growth from 2D to a 3D dimension we have recently developed a series of hydrogels where the porous particles are used as filler and to induce a better elasticity to the soft gel but also as a reservoir for the nutrients and differentiation factors for cells. We have demonstrated that the hybrid gels allows the cells to grow and differentiate and the materials have been already tested in vivo for different type of biomedical applications.All these results have been the subject of more than 30 publications, 2 patents, and the starting of a spin-off.
