In vivo processing of engineered nanoparticles (ENPs) was assessed using advanced imaging technologies coupled with simultaneous elemental analysis and acquisition of material phase changes and assessment of oxidation states of retained ENPs in tissue. Controlled uptake of ENPs was studied in rats to assess the dynamic chemical and/or physical breakdown of ENPs at the cellular and subcellular level in target tissues. The goal of the studies is to investigate cellular interactions of ENPs with their retention and biological and toxicological effects. Groups of rats were exposed to amorphous SiO2-ENPs areosols for 4 hrs/day, 5 days/week for 4 weeks with a 27 day post-exposure observation period at three different concentrations. Dose-dependent pulmonary inflammation in the rats was assessed in relation to the exposure time and dose. Prior analysis of the clearance kinetics using modeling of retained lung burden of ENPs showed a significant in vivo solubility which raised questions about underlying cellular mechanisms that result in the instability of the ENPs and related toxicity. High resolution imaging and examination of phagocytosed SiO2 ENPs in alveolar macrophages showed significant in vivo breakdown and transformation of the ENPs after inhalation. A comparison with the pristine precursor ENPs indicated that the original morphology and size was not retained in the lung. Contrary, the ENPs exhibited dissolution patterns and secondary reaction zones that had formed around the outskirts of the partially dissolving ENPs in the alveolar macrophages. Importantly, we observed that the in vivo processing resulted in second generation nanoparticles in the immediate vicinity of the bioprocessed ENPs. Moreover, ultra-high resolution imaging coupled with electron energy loss spectroscopy (EELS) demonstrated that there are continuing processes after ENPs uptake that cause release of ions and relocation of secondary phases which then result in the observed reaction zones. Further detailing the physio-chemical changes during bioprocessing of ENPs is a novel approach in nanotoxicology and may be an effective tool in understanding their subcellular and temporal fate that controls toxicity after environmental uptake.

In vivo bioprocessing of engineered nanoparticles after environmental uptake: Implications for health outcomes

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.