Luminescent Nano-Architectures for Theranostic Applications

Theranostic is a new paradigm in nanomedicine, aiming to design unique nanostructures where diagnostic and therapeutic tools are combined. The aim of my research work has been not only the design and preparation of nanomaterials for theranostic applications, focusing the investigation on dye doped Pluronic Silica nanoparticles (PluSNPs, a biocompatible silica core surrounded by a polymeric PEG shell, 25 nm hydrodynamic diameter), but also the development of methods based on fluorescence, for an improved characterization of such materials. Part of my research has been devoted to the improvement of the principal synthetic strategies to obtain Pluronic/Silica Nanoparticles able to act as efficient luminescent biomarkers integrating drug loading and release. A punctual characterization of such materials is not trivial due to their nano-confined high complexity. To this goal I have investigated a new fluorescence-based solvatochromic method, to map the polarity of neighboring nanoenviroments. This method evidenced the complex architecture of the Pluronic shell of this nanoparticles which can promote both hydrophilic and hydrophobic interactions. For a theranostic nanoparticle the interactions with the bioenvironment is of fundamental importance. To this goal I have studied: the interaction between PluSNPs and a fluorescent labeled hyaluronic acid (hydrophilic components of the extracellular matrix) and a novel fluorescence cross-correlation based method (2D-pCF) to map dynamical processes. In the first case fluorescence-based investigation has been used to follow the formation of hyaluronic acid/PluSNPs interactions to propose a model mechanism for the description of biomolecular corona, which can improve the nanoparticle cellular uptake. As important as the formation of these aggregates is the study of their motion and cellular localization. I have spent a period at University of California, Irvine, where Professor Enrico Gratton has developed a novel fluorescence cross-correlation based imaging method useful to map the dynamical processes and the trajectories of fluorescent nanostructures in cellular environments.