Ceria-Containing Hybrid Multilayered Microcapsules for Enhanced Cellular Internalisation with High Radioprotection Efficiency.

Cerium oxide nanoparticles (nanoceria) are believed to be the most versatile nanozyme, showing great promise for biomedical applications. At the same time, the controlled intracellular delivery of nanoceria remains an unresolved problem. Here, we have demonstrated the radioprotective effect of polyelectrolyte microcapsules modified with cerium oxide nanoparticles, which provide controlled loading and intracellular release. The optimal (both safe and uptake efficient) concentrations of ceria-containing microcapsules for human mesenchymal stem cells range from 1:10 to 1:20 cell-to-capsules ratio. We have revealed the molecular mechanisms of nanoceria radioprotective action on mesenchymal stem cells by assessing the level of intracellular reactive oxygen species (ROS), as well as by a detailed 96-genes expression analysis, featuring genes responsible for oxidative stress, mitochondrial metabolism, apoptosis, inflammation etc. Hybrid ceria-containing microcapsules have been shown to provide an indirect genoprotective effect, reducing the number of cytogenetic damages in irradiated cells. These findings give new insight into cerium oxide nanoparticles' protective action for living beings against ionising radiation.

Electromechanical and elastic probing of bacteria in a cell culture medium.

Rapid phenotype characterization and identification of cultured cells, which is needed for progress in tissue engineering and drug testing, requires an experimental technique that measures physical properties of cells with sub-micron resolution. Recently, band excitation piezoresponse force microscopy (BEPFM) has been proven useful for recognition and imaging of bacteria of different types in pure water. Here, the BEPFM method is performed for the first time on physiologically relevant electrolyte media, such as Dulbecco's phosphate-buffered saline (DPBS) and Dulbecco's modified Eagle's medium (DMEM). Distinct electromechanical responses for Micrococcus lysodeikticus (Gram-positive) and Pseudomonas fluorescens (Gram-negative) bacteria in DPBS are demonstrated. The results suggest that mechanical properties of the outer surface coating each bacterium, as well as the electrical double layer around them, are responsible for the BEPFM image formation mechanism in electrolyte media.

Protein-nanoparticle conjugates as potential therapeutic agents for the treatment of hyperlipidemia.

Hyperlipidemia, a condition associated with atherosclerosis, can develop because of the lack of low density lipoprotein (LDL) receptors in hepatocytes. Since injected polymeric nanoparticles are quickly taken up by the liver Kupffer cells, we hypothesize that it is possible to enhance LDL delivery to the liver through the use of LDL-absorbing nanoparticles. Here, we demonstrate the feasibility of the proposed approach in vitro. We used biodegradable and biocompatible polylactide nanoparticles (approximately 100 nm in diameter) with covalently attached apolipoprotein B100 antibody to adsorb LDLs at physiologically relevant concentrations. We showed that up to sixfold decreases of LDL levels can be achieved in vitro upon treatment of LDL suspensions (500 mg dl( - 1)) with anti-apoB100-nanoparticle conjugates. The study of the uptake of the antibody-nanoparticle-LDL complexes by cells was performed using a mouse macrophage cell line (RAW 264.7) as a model for liver Kupffer cells. We found that macrophages can quickly take up antibody-nanoparticle-LDL complexes and digest them within 24 h. No evidence of cytotoxicity was observed for the experimental conditions used in this study.

Double-layer mediated electromechanical response of amyloid fibrils in liquid environment.

Harnessing electrical bias-induced mechanical motion on the nanometer and molecular scale is a critical step toward understanding the fundamental mechanisms of redox processes and implementation of molecular electromechanical machines. Probing these phenomena in biomolecular systems requires electromechanical measurements be performed in liquid environments. Here we demonstrate the use of band excitation piezoresponse force microscopy for probing electromechanical coupling in amyloid fibrils. The approaches for separating the elastic and electromechanical contributions based on functional fits and multivariate statistical analysis are presented. We demonstrate that in the bulk of the fibril the electromechanical response is dominated by double-layer effects (consistent with shear piezoelectricity of biomolecules), while a number of electromechanically active hot spots possibly related to structural defects are observed.

Functional recognition imaging using artificial neural networks: applications to rapid cellular identification via broadband electromechanical response.

Functional recognition imaging in scanning probe microscopy (SPM) using artificial neural network identification is demonstrated. This approach utilizes statistical analysis of complex SPM responses at a single spatial location to identify the target behavior, which is reminiscent of associative thinking in the human brain, obviating the need for analytical models. We demonstrate, as an example of recognition imaging, rapid identification of cellular organisms using the difference in electromechanical activity over a broad frequency range. Single-pixel identification of model Micrococcus lysodeikticus and Pseudomonas fluorescens bacteria is achieved, demonstrating the viability of the method.