Membrane-bound heat shock protein mHsp70 is required for migration and invasion of brain tumors.

Molecular chaperones, especially 70 kDa heat shock protein, in addition to their intracellular localization in cancer cells, can be exposed on the surface of the plasma membrane. We report that the membrane-associated chaperone mHsp70 of malignant brain tumors is required for high migratory and invasive activity of cancer cells. Live-cell inverted confocal microscopy of tumor samples from adult (n=23) and pediatric (n=9) neurooncological patients showed pronounced protein expression on the membrane, especially in the perifocal zone. Mass-spectrometry analysis of lipid rafts isolated from tumor cells confirmed the presence of the protein in chaperone cluster (including representatives of other families such as Hsp70, Hsc70, Hsp105, Hsp90), which in turn, during interactome analysis, was associated with proteins involved in cell migration (e.g., Rac1, RhoC, myosin-9). The use of small-molecule inhibitors of HSP70 (PES, JG-98) led to a significant decrease in the invasive potential of cells isolated from a tumor sample of patients, which indicates the role of the chaperone in invasion. Moreover, the use of HSP70 inhibitors in animal models of orthotopic brain tumors significantly delayed tumor progression, which was accompanied by an increase in overall survival. Data demonstrate that chaperone inhibitors, particularly JG-98, disrupt the function of mHsp70, thereby providing an opportunity to better understand the diverse functions of this protein and offer aid in the development of novel cancer therapies.

Plasmonic Nanocomposites of ZnO-Ag Produced by Laser Ablation and Their Photocatalytic Destruction of Rhodamine, Tetracycline and Phenol.

Hydrosphere pollution by organic pollutants of different nature (persistent dyes, phenols, herbicides, antibiotics, etc.) is one of the urgent ecological problems facing humankind these days. The task of water purification from such pollutants can be effectively solved with the help of modern photocatalytic technologies. This article is devoted to the study of photocatalytic properties of composite catalysts based on ZnO modified with plasmonic Ag nanoparticles. All materials were obtained by laser synthesis in liquid and differed by their silver content and preparation conditions, such as additional laser irradiation and/or annealing of produced powders. The prepared ZnO-Ag powders were investigated by electron microscopy, X-ray diffraction and UV-Vis spectroscopy. Photocatalytic tests were carried out with well- known test molecules in water (persistent dye rhodamine B, phenol and common antibiotic tetracycline) using LED light sources with wavelengths of 375 and 410 nm. The introduction of small concentrations (up to 1%) of plasmonic Ag nanoparticles is shown to increase the efficiency of the ZnO photocatalyst by expanding its spectral range. Both the preparation conditions and material composition were optimized to obtain composite photocatalysts with the highest efficiency. Finally, the operation mechanisms of the material with different distribution of silver are discussed.

Passing of Nanocarriers across the Histohematic Barriers: Current Approaches for Tumor Theranostics.

Over the past several decades, nanocarriers have demonstrated diagnostic and therapeutic (i.e., theranostic) potencies in translational oncology, and some agents have been further translated into clinical trials. However, the practical application of nanoparticle-based medicine in living organisms is limited by physiological barriers (blood-tissue barriers), which significantly hampers the transport of nanoparticles from the blood into the tumor tissue. This review focuses on several approaches that facilitate the translocation of nanoparticles across blood-tissue barriers (BTBs) to efficiently accumulate in the tumor. To overcome the challenge of BTBs, several methods have been proposed, including the functionalization of particle surfaces with cell-penetrating peptides (e.g., TAT, SynB1, penetratin, R8, RGD, angiopep-2), which increases the passing of particles across tissue barriers. Another promising strategy could be based either on the application of various chemical agents (e.g., efflux pump inhibitors, disruptors of tight junctions, etc.) or physical methods (e.g., magnetic field, electroporation, photoacoustic cavitation, etc.), which have been shown to further increase the permeability of barriers.

Antibacterial Ferroelectric Hybrid Membranes Fabricated via Electrospinning for Wound Healing.

In the present study, wound healing ferroelectric membranes doped with zinc oxide nanoparticles were fabricated from vinylidene fluoride-tetrafluoroethylene copolymer and polyvinylpyrrolidone using the electrospinning technique. Five different ratios of vinylidene fluoride-tetrafluoroethylene to polyvinylpyrrolidone were used to control the properties of the membranes at a constant zinc oxide nanoparticle content. It was found that an increase of polyvinylpyrrolidone content leads to a decrease of the spinning solution conductivity and viscosity, causing a decrease of the average fiber diameter and reducing their strength and elongation. By means of X-ray diffraction and infrared spectroscopy, it was revealed that increased polyvinylpyrrolidone content leads to difficulty in crystallization of the vinylidene fluoride-tetrafluoroethylene copolymer in the ferroelectric ß-phase in membranes. Changing the ratio of vinylidene fluoride-tetrafluoroethylene copolymer and polyvinylpyrrolidone with a constant content of zinc oxide nanoparticles is an effective approach to control the antibacterial properties of membranes towards Staphylococcus aureus. After carrying out in vivo experiments, we found that ferroelectric hybrid membranes, containing from five to ten mass percent of PVP, have the greatest wound-healing effect for the healing of purulent wounds.

Structure and Properties of Biodegradable PLLA/ZnO Composite Membrane Produced via Electrospinning.

These days, composite materials based on polymers and inorganic nanoparticles (NPs) are widely used in optoelectronics and biomedicine. In this work, composite membranes of polylactic acid and ZnO NPs containing 5-40 wt.% of the latter NPs were produced by means of electrospinning. For the first time, polymer material loaded with up to 40 wt.% of ZnO NPs (produced via laser ablation in air and having non-modified surface) was used to prepare fiber-based composite membranes. The morphology, phase composition, mechanical, spectral and antibacterial properties of the membranes were tested by a set of analytical techniques including SEM, XRD, FTIR, UV-vis, and photoluminescence spectroscopy. Antibacterial activity of the materials was evaluated following standard procedures (ISO 20743:2013) and using S. aureus and E. coli bacteria. It is shown that incorporation of 5-10 wt.% of NPs led to improved mechanical properties of the composite membranes, while further increase of ZnO content up to 20 wt.% and above resulted in their noticeable deterioration. At the same time, the antibacterial properties of ZnO-rich membranes were more pronounced, which is explained by a larger number of surface-exposed ZnO NPs, in addition to those embedded into the bulk of fiber material.

Comparative Study of Physicochemical and Antibacterial Properties of ZnO Nanoparticles Prepared by Laser Ablation of Zn Target in Water and Air.

Here, we report on ZnO nanoparticles (NPs) generated by nanosecond pulsed laser (Nd:YAG, 1064 nm) through ablation of metallic Zn target in water and air and their comparative analysis as potential nanomaterials for biomedical applications. The prepared nanomaterials were carefully characterized in terms of their structure, composition, morphology and defects. It was found that in addition to the main wurtzite ZnO phase, which is conventionally prepared and reported by others, the sample laser generated in air also contained some amount of monoclinic zinc hydroxynitrate. Both nanomaterials were then used to modify model wound dressings based on biodegradable poly l-lactic acid. The as-prepared model dressings were tested as biomedical materials with bactericidal properties towards S. aureus and E. coli strains. The advantages of the NPs prepared in air over their counterparts generated in water found in this work are discussed.