Biphasic water-oil systems for functional augmentation of probiotic Lactobacillus acidophilus nanoencapsulated in luteolin-Fe3+ shells.

Single-cell nanoencapsulation (SCNE) has great potential in the enhancement of therapeutic effects of probiotic microbes. However, the material scope has been limited to water-soluble compounds to avoid non-biocompatible organic solvents that are harmful to living cells. In this work, the SCNE of probiotic Lactobacillus acidophilus with water-insoluble luteolin and Fe3+ ions is achieved by the vortex-assisted, biphasic water-oil system. The process creates L. acidophilus nanoencapsulated in the luteolin-Fe3+ shells that empower the cells with extrinsic properties, such as resistance to lysozyme attack, anti-ROS ability, and α-amylase-inhibition activity, as well as sustaining viability under acidic conditions. The proposed protocol, embracing water-insoluble flavonoids as shell components in SCNE, will be an advanced add-on to the chemical toolbox for the manipulation of living cells at the single-cell level.

A Micrometric Transformer: Compositional Nanoshell Transformation of Fe3+ -Trimesic-Acid Complex with Concomitant Payload Release in Cell-in-Catalytic-Shell Nanobiohybrids.

Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme-embedded nanoshell of Fe3+ -trimesic acid complex to an iron phosphate shell in phosphate-containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin-2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell-in-shell nanobiohybrids that can interact with their surroundings in active and adaptive ways.

Tandem-biocatalysis reactors constructed by topological evolution of CaCO3 particles into hollow metal hydroxide spheres.

Despite remarkable advances in the design and synthesis of hollow inorganic spheres (HISs), the harsh synthetic conditions have precluded the applications of HISs to biochemical and biological fields. Herein we report a biocompatible strategy for synthesizing metal hydroxide HISs (MH-HISs) by simply mixing CaCO3 particles with metal ions in water. The ion-exchange reaction between Ca2+ and metal ions leads to the structural and chemical evolution from solid CaCO3 particles to hollow MH-HISs via core-shell and yolk-shell structures, while enabling the encapsulation of enzymes to the shells without loss of catalytic activities. The biocompatible protocol makes multienzymatic cascade reactions achievable, with great recyclability due to mechanical durability of MH-HISs.

A Natural Virucidal and Microbicidal Spray Based on Polyphenol-Iron Sols.

Numerous disinfection methods have been developed to reduce the transmission of infectious diseases that threaten human health. However, it still remains elusively challenging to develop eco-friendly and cost-effective methods that deactivate a wide range of pathogens, from viruses to bacteria and fungi, without doing any harm to humans or the environment. Herein we report a natural spraying protocol, based on a water-dispersible supramolecular sol of nature-derived tannic acid (TA) and Fe3+, which is easy-to-use and low-cost. Our formulation effectively deactivates viruses (influenza A viruses, SARS-CoV-2, and human rhinovirus) as well as suppressing the growth and spread of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Acinetobacter baumannii) and fungi (Pleurotus ostreatus and Trichophyton rubrum). Its versatile applicability in a real-life setting is also demonstrated against microorganisms present on the surfaces of common household items (e.g., air filter membranes, disposable face masks, kitchen sinks, mobile phones, refrigerators, and toilet seats).

Cytoprotection of Probiotic Lactobacillus acidophilus with Artificial Nanoshells of Nature-Derived Eggshell Membrane Hydrolysates and Coffee Melanoidins in Single-Cell Nanoencapsulation.

One-step fabrication method for thin films and shells is developed with nature-derived eggshell membrane hydrolysates (ESMHs) and coffee melanoidins (CMs) that have been discarded as food waste. The nature-derived polymeric materials, ESMHs and CMs, prove highly biocompatible with living cells, and the one-step method enables cytocompatible construction of cell-in-shell nanobiohybrid structures. Nanometric ESMH-CM shells are formed on individual probiotic Lactobacillus acidophilus, without any noticeable decrease in viability, and the ESMH-CM shells effectively protected L. acidophilus in the simulated gastric fluid (SGF). The cytoprotection power is further enhanced by Fe3+-mediated shell augmentation. For example, after 2 h of incubation in SGF, the viability of native L. acidophilus is 30%, whereas nanoencapsulated L. acidophilus, armed with the Fe3+-fortified ESMH-CM shells, show 79% in viability. The simple, time-efficient, and easy-to-process method developed in this work would contribute to many technological developments, including microbial biotherapeutics, as well as waste upcycling.

Vortex-assisted, nanoarchitectonic manipulation of microparticles with flavonoid-Fe3+ complex in biphasic water-oil systems.

Coordination-driven self-assembly of metal-ligand complexes is a powerful nanoarchitectonic tool for particle engineering, but its usability is limited when using two immiscible coating components. This paper reports that simple vortexing of a biphasic system of Fe3+ ions in water and flavonoids in oil forms nanoshells on individual particles, thereby enabling the utilization of water-insoluble ligands as coating materials. Mechanistic studies suggest that the biphasic mass-transfer equilibrium of flavonoid-Fe3+ species controls the shell formation, with the oil phase acting as a reservoir of coating precursors for continuous coating. The versatility and convenience of our method expand the chemical toolbox for modulating particle-material interfaces.

Cell-in-Catalytic-Shell Nanoarchitectonics: Catalytic Empowerment of Individual Living Cells by Single-Cell Nanoencapsulation.

Cell-in-shell biohybrid structures, synthesized by encapsulating individual living cells with exogenous materials, have emerged as exciting functional entities for engineered living materials, with emergent properties outside the scope of biochemical modifications. Artificial exoskeletons have, to date, provided physicochemical shelters to the cells inside in the first stage of technological development, and further advances in the field demand catalytically empowered, cellular hybrid systems that augment the biological functions of cells and even introduce completely new functions to the cells. This work describes a facile and generalizable strategy for empowering living cells with extrinsic catalytic capability through nanoencapsulation of living cells with a supramolecular metal-organic complex of Fe3+ and benzene-1,3,5-tricarboxylic acid (BTC). A series of enzymes are embedded in situ, without loss of catalytic activity, in the Fe3+ -BTC shells, not to mention the superior characteristics of cytocompatible and rapid shell-forming processes. The nanoshell enhances the catalytic efficiency of multienzymatic cascade reactions by confining reaction intermediates to its internal voids and the nanoencapsulated cells acquire exogenous biochemical functions, including enzymatic cleavage of lethal octyl-ß-d-glucopyranoside into d-glucose, with autonomous cytoprotection. The system will provide a versatile, nanoarchitectonic tool for interfacing biological cells with functional materials, especially for catalytic bioempowerment of living cells.

Enzyme-Mediated Kinetic Control of Fe3+-Tannic Acid Complexation for Interface Engineering.

Supramolecular self-assembly of Fe3+ and tannic acid (TA) has received great attention in the fields of materials science and interface engineering because of its exceptional surface coating properties. Although advances in coating strategies often suggest that kinetics in the generation of interface-active Fe3+-TA species is deeply involved in the film formation, there is no acceptable elucidation for the coating process. In this work, we developed the enzyme-mediated kinetic control of Fe2+ oxidation to Fe3+ in a Fe2+-TA complex in the iron-gall-ink-revisited coating method. Specifically, hydrogen peroxide, produced in the glucose oxidase (GOx)-catalyzed reaction of d-glucose, accelerated Fe2+ oxidation, and the optimized kinetics profoundly facilitated the film formation to be about 9 times thicker. We also proposed a perspective considering the coating process as nucleation and growth. From this viewpoint, the kinetics in the generation of interface-active Fe3+-TA species should be optimized because it determines whether the interface-active species forms a film on the substrate (i.e., heterogeneous nucleation and film growth) or flocculates in solution (i.e., homogeneous nucleation and particle growth). Moreover, GOx was concomitantly embedded into the Fe3+-TA films with sustained catalytic activities, and the GOx-mediated coating system was delightfully adapted to catalytic single-cell nanoencapsulation.

Reversed Anionic Hofmeister Effect in Metal-Phenolic-Based Film Formation.

Although metal-phenolic species have emerged as one of the versatile material-independent-coating materials, providing attractive tools for interface engineering, mechanistic understanding of their film formation and growth still remains largely unexplored. Especially, the anions have been overlooked despite their high concentration in the coating solution. Considering that the anions are critical in the reactivity of metal-organic complex and the formation and/or property of functional materials, we investigated the anionic effects on the characteristics of film formation, such as film thickness and properties, in the Fe3+-tannic acid coating. We found that the film characteristics were strongly dictated by the counteranions (e.g., SO42-, Cl-, and Br-) of the Fe3+ ion. Specifically, the film thickness and properties (i.e., mechanical modulus, permeability, and stability) followed the reversed anionic Hofmeister series (Br- > Cl- > SO42-). Mechanistic studies suggested that more chaotropic anions, such as Br-, might induce a more widely extended structure of the Fe3+-TA complexes in the coating solution, leading to thicker, harder, but more porous films. The reversed anionic Hofmeister effect was further confirmed by the additive effects of various sodium salts (NaF, NaCl, NaBr, and NaClO4).

Ascorbic acid-mediated reductive disassembly of Fe3+-tannic acid shells in degradable single-cell nanoencapsulation.

Rapid degradation of Fe3+-tannic acid films is achieved under mild conditions via ascorbic acid-mediated Fe3+ reduction, which overcomes the problems in the disassembly of a metal-organic complex including slow reaction rates and reaction incompatibility with living cells. The strategy of reductive disassembly is applied to degradable single-cell nanoencapsulation, providing an advanced tool for tightly controlling and manipulating the cell-material interface.

Fabrication and Characterization of Neurocompatible Ulvan-Based Layer-by-Layer Films.

Construction of extracellular matrix-mimetic nanofilms has considerable potential in biomedical and nanomedicinal fields. In this work, we fabricated neurocompatible layer-by-layer (LbL) films based on ulvan (ULV), a highly sulfated polysaccharide having compositional similarity to glycosaminoglycans that play important functional roles in the brain. ULV was durably assembled as a film with chitosan, another marine-derived polysaccharide, and the film enabled the stable adhesion of primary hippocampal neurons with high viability, comparable to the conventional poly-d-lysine surface. Notably, the ULV-based LbL films accelerated neurite outgrowth and selectively suppressed the adhesion of astrocytes, highlighting its potential as an advanced platform for neural implants and devices.

Enzymatically degradable, starch-based layer-by-layer films: application to cytocompatible single-cell nanoencapsulation.

The build-up and degradation of cytocompatible nanofilms in a controlled fashion have great potential in biomedical and nanomedicinal fields, including single-cell nanoencapsulation (SCNE). Herein, we report the fabrication of biodegradable films of cationic starch (c-ST) and anionic alginate (ALG) by electrostatically driven layer-by-layer (LbL) assembly technology and its application to the SCNE. The [c-ST/ALG] multilayer nanofilms, assembled either on individual Saccharomyces cerevisiae or on the 2D flat gold surface, degrade on demand, in a cytocompatible fashion, via treatment with α-amylase. Their degradation profiles are investigated, while systematically changing the α-amylase concentration, by several surface characterization techniques, including quartz crystal microbalance with dissipation monitoring (QCM-D) and ellipsometry. DNA incorporation in the LbL nanofilms and its controlled release, upon exposure of the nanofilms to an aqueous α-amylase solution, are demonstrated. The highly cytocompatible nature of the film-forming and -degrading conditions is assessed in the c-ST/ALG-shell formation and degradation of S. cerevisiae. We envisage that the cytocompatible, enzymatic degradation of c-ST-based nanofilms paves the way for developing advanced biomedical devices with programmed dissolution in vivo.

Synthetic Strategies for (-)-Cannabidiol and Its Structural Analogs.

(-)-Cannabidiol ((-)-CBD), a non-psychoactive phytocannabinoid from Cannabis, and its structural analogs have received growing attention in recent years because of their potential therapeutic benefits, including neuroprotective, anti-epileptic, anti-inflammatory, anxiolytic, and anti-cancer properties. (-)-CBD and its analogs have been obtained mainly based on extraction from the natural source; however, the conventional extraction-based methods have some drawbacks, such as poor quality control along with purification difficulty. Chemical-synthetic strategies for (-)-CBD could tackle these issues, and, additionally, generate novel (-)-CBD analogs that exhibit advanced biological activities. This review concisely summarizes the historic and recent milestones in the synthetic strategies for (-)-CBD and its analogs.

Acoustic radiation force impulse elastography for hepatocellular carcinoma-associated radiofrequency ablation.

AIM: To evaluate the potential usefulness of acoustic radiation force impulse (ARFI) images for evaluation of hepatocellular carcinomas (HCC)-associated radiofrequency ablation. METHODS: From January 2010 to June 2010, a total of 38 patients with HCC including recurred HCCs after RFA underwent ARFI elastography. The brightness of tumor was checked and the shear wave velocity was measured for the quantification of stiffness. According to the brightness, the tumors were classified as brighter, same color and darker compared with adjacent parenchyma. Using the same methods, 8 patients with recurred HCCs after RFA state were evaluated about the brightness compared with adjacent RFA ablation area. RESULTS: In the 38 patients with HCCs, 20 (52.6%) were brighter than surrounding cirrhotic parenchyma. Another 13 (34.2%) were darker. The others (5 cases, 13.2%) were seen as the same color as the adjacent liver parenchyma. Post-RFA lesions were darker than previous tumor and surrounding parenchyma in all 38 cases. However, recurred HCCs were brighter than the treated site in all 8 cases. CONCLUSION: Using ARFI technique is helpful for differential diagnosis in order to detect recurred HCCs more easily in patients with confusing status.