Search

Circulating tumor cells (CTCs) are some of the key culprits that cause cancer metastasis and metastasis-related deaths. These cells exist in a dynamic microenvironment where they experience fluid shear stress (FSS), and the CTCs that survive FSS are considered to be highly metastatic and stem cell-like. Biophysical stresses such as FSS are also known to cause the production of extracellular vesicles (EVs) that can facilitate cell-cell communication by carrying biomolecular cargos such as microRNAs. Here, we hypothesized that physiological FSS will impact the yield of EV production, and that these EVs will have biomolecules that transform the recipient cells. The EVs were isolated using direct flow filtration with and without FSS from the MDA-MB-231 cancer cell line, and the expression of key stemness-related genes and microRNAs was characterized. There was a significantly increased yield of EVs under FSS. These EVs also contained significantly increased levels of miR-21, which was previously implicated to promote metastatic progression and chemotherapeutic resistance. When these EVs from FSS were introduced to MCF-7 cancer cells, the recipient cells had a significant increase in their stem-like gene expression and CD44 + /CD24 - cancer stem cell-like subpopulation. There was also a correlated increased proliferation along with an increased ATP production. Together, these findings indicate that the presence of physiological FSS can directly influence the EVs' production and their contents, and that the EV-mediated transfer of miR-21 can have an important role in FSS-existing contexts, such as in cancer metastasis.

Extracellular vesicles (EVs) have shown great potential as cell-free therapeutics and biomimetic nanocarriers for drug delivery. However, the potential of EVs is limited by scalable, reproducible production and in vivo tracking after delivery. Here, we report the preparation of quercetin-iron complex nanoparticle-loaded EVs derived from a breast cancer cell line, MDA-MB-231br, using direct flow filtration. The morphology and size of the nanoparticle-loaded EVs were characterized using transmission electron microscopy and dynamic light scattering. The SDS-PAGE gel electrophoresis of those EVs showed several protein bands in the range of 20-100 kDa. The analysis of EV protein markers by a semi-quantitative antibody array confirmed the presence of several typical EV markers, such as ALIX, TSG101, CD63, and CD81. Our EV yield quantification suggested a significant yield increase in direct flow filtration compared with ultracentrifugation. Subsequently, we compared the cellular uptake behaviors of nanoparticle-loaded EVs with free nanoparticles using MDA-MB-231br cell line. Iron staining studies indicated that free nanoparticles were taken up by cells via endocytosis and localized at a certain area within the cells while uniform iron staining across cells was observed for cells treated with nanoparticle-loaded EVs. Our studies demonstrate the feasibility of using direct flow filtration for the production of nanoparticle-loaded EVs from cancer cells. The cellular uptake studies suggested the possibility of deeper penetration of the nanocarriers because the cancer cells readily took up the quercetin-iron complex nanoparticles, and then released nanoparticle-loaded EVs, which can be further delivered to regional cells.

Temperature swing solvent extraction (TSSE) utilizes an amine solvent with temperature-dependent water solubility to dissolve water at a lower temperature to concentrate or crystallize the brine and the phases are separated. Then, the water in solvent mixture is heated to reduce water solubility and cause phase separation between the solvent and water. The solvent and de-salted water phases are separated, and the regenerated solvent can be recycled. Issues with current TSSE solvents include the high solvent in water solubility and the high solvent volatility. This project used the highly tunable platform molecule imidazole to create two 1-butylimidazole isomers, specifically 1-propyl-4(5)-methylimidazole, to test their effectiveness for TSSE. The imidazoles take in more water than their current state-of-the-art counterparts, but do not desalinate the product water and dissolve in water at higher concentrations. Thus, while imidazoles make intriguing candidates for TSSE, further work is needed to understand how to design imidazoles that will be useful for TSSE applications.

Membranes used for desalination still face challenges during operation. One of these challenges is the buildup of salt ions at the membrane surface. This is known as concentration polarization, and it has a negative effect on membrane water permeance and salt rejection. In an attempt to decrease concentration polarization, a line-and-groove nanopattern was applied to a nanofiltration (NF) membrane. Aqueous sodium sulfate (Na 2 SO 4 ) solutions were used to test the rejection and permeance of both pristine and patterned membranes. It was found that the nanopatterns did not reduce but increased the concentration polarization at the membrane surface. Based on these studies, different pattern shapes and sizes should be investigated to gain a fundamental understanding of the influence of pattern size and shape on concentration polarization.

In this paper, we discuss the effect of alcohol contact on the transport properties of thin-film composite reverse osmosis membranes. Five commercial membranes were studied to quantify the changes in water permeance and sodium chloride rejection from contact with five C1-C4 monohydric, linear alcohols. Water permeance generally increased without decreasing rejection after short-term contact. The extent of these changes depends on the membrane and alcohol used. Young's modulus measurements showed decreased stiffness of the active layer after contacting the membranes with alcohol, suggesting plasticization. Data analysis using a dual-mode sorption model identified positive correlations of the initial water permeance, as well as the change in free energy of mixing between water and the alcohols, with the increase in water permeance after alcohol contact. We suggest that the mixing of water with the alcohols facilitates alcohol penetration into the active layer, likely by disrupting inter-chain hydrogen bonds, thus increasing the free volume for water permeation. Our studies provide a modeling framework to estimate the changes in transport properties after short-term contact with C1-C4 alcohols.

Selective desalination through nanofiltration (NF) is of great interest for many industrial applications including reuse of power plant scrubber wastewater and treatment of water containing high concentrations of TDS (total dissolved solids). This work seeks to understand the effect ion interactions at the membrane interface have on rejection and flux performance of charged NF membranes. NF membranes were also effective for low energy desalination of scrubber wastewater from Georgia Power Plant Bowen, composed primarily of Ca 2+ , Mg 2+ , Cl - , and SO 4 2- . As NF membranes have the capability for selective separations, 80% water recovery was achieved experimentally while maintaining an overall rejection of over 60% for Ca 2+ and Cl - . The occurrence of CaSO 4 precipitation at high water recovery was observed. The effect of precipitation on osmotic pressure and the effect of Cl - counterions on increasing gypsum solubility were explored for water recovery operation. This work expands on a previous work on the topics of desalination of multi-ionic solutions by incorporating the use of large scale membrane modules (0.59 m 2 ) with several synthetic solutions as well as actual scrubber water containing precipitating elements, Ca 2+ and SO 4 2- . It was observed that the spiral wound membrane modules maintained a stable water permeability over the 144 day course of tests., Competing Interests: The authors declare no competing financial interest.