Multi-functionalization of micro- and nanoparticles for cancer theranostics

Abstract

[eng] Supramolecular chemistry is regarded as a tool to build up nanomaterials through a bottom-up approach. As such, it includes the bio-functionalization of inorganic and metallic surfaces with natural and synthetic receptors to obtain micro-nanotools capable of interacting with biological material and sensing its function, which is the main topic of this research project. Thus, its overall objective is to prepare micro- and nanotools acting as sensors to monitor different cellular parameters in living cells, and deliverers specifically for diagnosis and therapy in cancer cells (theranostics). For this purpose, we used micro- and nanoparticles as substrates, made up of polysilicon or polysilicon-gold and gold nanoparticles, and functionalized them with (bio)molecules. The first objective is to develop a novel microtool for cell adhesion. For this purpose we worked with specially designed polysilicon microparticles of different shapes and sizes, which were chemically modified, to sense carbohydrates present on tumour cell membranes. Chemical modification of these microparticles were performed using lectins, carbohydrate binding proteins which specifically recognizes the carbohydrates present on the cell membranes of specific cells. In the final step, in vitro experiments were carried out in HeLa or Dictyostelium discoideum (Dicty), to assess their ability of adhesion to the cell membrane. In the second objective, the primary goal is to sense intracellular pH in living cells using bi-functional microparticles, in order to differentiate between cancer cells and normal cells. Therefore, for this study we immobilized different pH dependent fluorophores on to a mono-(polysilicon) or bi-functional (polysilicon-gold) microparticles for sensing pH, which were characterized using various techniques. The third objective is the generation and sensing of Reactive oxygen species (ROS) using a bio-photosensitizer for photodynamic therapy. The main goal is to develop and optimize a protocol for immobilizing ROS generator and a ROS sensor on to bi-functional microparticle to sense the production of ROS. The fourth objective is to deliver anionic drugs using gold nanoparticles synthesized using imidazolium based macrocycles. These nanoparticles showed successful incorporation of a model anionic drug and its kinetic release profile was measured at different pHs which showed that the synthesized gold nanoparticles could be used for local drug delivery applications.