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The impact on human health of long-term exposure to low doses of silver nanoparticles (AgNPs) remains understudied. Cellular studies have shown the intracellular dissolution of AgNPs within endolysosomes followed by Ag(i) binding to biomolecular thiolate-containing molecules. However, the precise subcellular distribution of Ag(i) and the nature of the disrupted physiological pathways remained unknown. Novel imaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards a perinuclear location and a nuclear transfer of Ag(i) species with accumulation in the nucleoli. These Ag(i) species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in low dose exposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.

Liver is pivotal in organism metabolism. This organ is receiving nutriments from the portal vein and then storing, metabolizing, distributing in the circulation or excreting excess and xenobiotics in bile. Liver architecture and hepatocyte polarization are crucial to achieve these functions. To study these mechanisms in details, relevant cell culture systems are required, which is not the case with standard 2D cell culture. Besides, primary hepatocytes rapidly de-differenciate making them inefficient in forming physiological system. Herein, we used an hepatoma-derived cell line to produce matrix-free hepatic spheroids and developed an integrated structural cell biology methodology by combining light sheet fluorescence microscopy and 3D electron microscopy to study their function and structure. Within these spheroids, hepatocytes polarize and organize to form bile canaliculi active for both organics and inorganics excretion. Besides, live imaging revealed the high dynamic of actin networks in basal membranes compared to their high stability in the apical pole that constitutes bile canaliculi. Finally, the first structure of active bile canaliculi was solved at nm resolution and showed the very high density of microvilli coming from all cells constituting the canaliculus. Therefore, this study is the first comprehensive and in-depth functional and structural study of bile canaliculi in a physiological-relevant context.

Increasing production of nanomaterials makes the study of nanoparticles fate in the environment of immediate interest. Nanomaterials are known to radically change their properties when released into the environment. In this work, the ability of nanoparticles to form stable dispersions in physiological solutions has been demonstrated. The dispersions were prepared by mixing nanopowders of zinc (13.58 m2/g), copper (24.66 m2/g), aluminum oxides (54.75 m2/g), and zirconium dioxide (8.10 m2/g) with phosphate buffered saline, an isotonic solution of glucose and artificial lysosomal fluid. With the help of laser diffraction method and transmission electron microscopy it was shown that unstable suspensions (with the dispersoid size of 6...49 μm) and aggregative-stable lyosols (with the particles size of 20...300 nm) were formed in dispersions of nanoparticles in physiological media.

When nanoparticles get into a living body, they interact with body fluids. This study shows high physicochemical persistence of electroexplosive aluminum nanoparticles in physiological solutions simulating body fluids: Artificial Sweat (ASw), Simulated Saliva (SS), Simulated Gastric Fluid (SGF), and Artificial Alveolar Fluid (AAF). It has been demonstrated that after 14 days of exposure in ASw SS SGF AAF solutions, the average size of initial 90 nm nanoparticles became 90 100 230 90 nm, and the average size of initial 5 μm agglomerates became 1.6 0.9 1.0 3.0 μm, respectively. According to s SEM data, the exposed particles retained their spherical shape. With the help of the X-ray phase analysis it was shown that the oxide/hydroxide phase content in nanoparticles did not increase. It has been concluded that highly-reactive aluminum nanoparticles are capable to retain their phase composition, dispersion, and morphology in synthetic body fluids.