Physicochemical characterization and biocompatibility studies of persistent luminescence nanoparticles for preclinical diagnosis applications

Abstract

Nowadays engineered nanoparticles surround us, leading to many and highly valuable applications in different domains. Thanks to their unique properties they are revolutionizing and pushing up varied research areas including biomedical, material, physics and chemistry sciences, and thereby our society. Nevertheless, those properties are hardly dependent on the nature, size, shape, surface chemistry and chemical environment of these materials. The use of nanoparticles for biomedical applications implies the knowledge of their physicochemical parameters in physiologically relevant media. Zinc gallate nanoparticles doped with chromium (ZnGa1.995Cr0.005O4) are innovative persistent luminescence materials with particular optical properties allowing their use for in vivo imaging. They offer the promise of revolutionary tools for biological imaging with applications such as cellular tracking or tumor detection. They can be excited in the tissue transparency window by visible photons and emit light for hours after the end of the excitation. This allows observing the probe without any time constraints nor autofluorescence signals produced by biological tissues when using fluorescent probes. In the first chapter, a brief review describing the relevance of the ZnGa1.995Cr0.005O4 nanoparticles and their applications is presented. Thereafter, the nanoparticle functionalization effects on their physico-chemical properties and on their colloidal stability and applications are described. Some important aspects about NPS pharmacokinetic and their biocompatibility are also presented in order to lay the groundwork for the toxicity studies presented in Chapters VI and VII. Finally, the state of the art and trends about the characterization of NPS by means of electrokinetic methodologies and the parameters obtained from the electrophoretic profiles are reviewed with emphasis on the NPs characterization for biomedical applications and their interactions with biomolecules. Modification of the surface of these nanoparticles is essential to be colloidally stable not only for cell targeting applications but also for proper distribution in living organisms. The use of different methods for controlling and characterizing the functionalization process is imperative to better understand the subsequent interactions with biological elements. The optimization of the ZnGa1.995Cr0.005O4 synthesis with various functional groups on their surface (-OH, aminosilane and PEG) and their physic-chemical characterization have been explored for the first time in this work by means of dynamic light scattering, laser Doppler electrophoresis in combination with capillary electrophoresis. The results are presented in Chapter II. Special interest was focused in the latter method in order to evaluate its potential for the evaluation of colloidal and chemical properties and stability of functionalized nanoparticles. The hydrodynamic diameter, zeta potential, electrophoretic dispersion, stability over time and aggregation state of persistent luminescence nanoparticles under physiological-based conditions have been studied for each functional state. This thorough control increases our knowledge on these nanoparticles for subsequent interactions and toxicological studies and ultimately medical application.