Title: Multiscale approaches to monitor the long-term life fate and bio processing of anticancer heat-mediating nanoparticles and their optimization

Abstract

In recent years, increasing interest has risen toward innovative nanomaterials engineering and tailor-made applications of nanomedicine compositions. As a result, the follow-up of potential degradation of these complex nanohybrids has become central for their future medical use. We investigated the fate of several anticancer heat-mediating nanoparticles upon interaction with different biological model systems using thermometric and magnetic measurements, as well as methods of structural analysis (XANES/EXAFS spectroscopy and HR-TEM), as direct and quantitative assessment of the bio transformations in the tissues. Furthermore, nanotoxicology and gene expression studies addressed the impact of the nanoparticles on the cell metabolism, the cell viability or their differentiation. All nanostructures analyzed underwent profound biotransformation that triggered an adaptation of the cellular metabolism to the released metals. Besides, a massive intracellular remodeling of the nanoparticles could originate newly formed biogenic nanostructures and, depending from their composition, can preserve or not the therapeutic efficacy. Both nanomaterials’ intracellular performances and their biocompatibility including their ultimate fate inside the human body need to be extensively monitored in long-term analysis in order to ensure their applicability into the clinic. Furthermore, the therapeutic potential of heat-generating nanoparticles is limited to a specific temporal period that is often overlooked but is central for their medical applications.