Π-Π interactions stabilize PeptoMicelle-based formulations of Pretomanid derivatives leading to promising therapy against tuberculosis in zebrafish and mouse models.

Tuberculosis is the deadliest bacterial disease globally, threatening the lives of millions every year. New antibiotic therapies that can shorten the duration of treatment, improve cure rates, and impede the development of drug resistance are desperately needed. Here, we used polymeric micelles to encapsulate four second-generation derivatives of the antitubercular drug pretomanid that had previously displayed much better in vivo activity against Mycobacterium tuberculosis than pretomanid itself.

Temperature Controlled Mechanical Reinforcement of Polyacrylate Films Containing Nematic Liquid Crystals.

This investigation reports on the thermomechanical properties of Poly-tripropyleneglycoldiacrylate (Poly-TPGDA)/liquid crystal (LC) blends, developed via free radical polymerization processes, which are induced by Electron Beam (EB) and Ultraviolet (UV) radiation. The EB-cured Poly-TPGDA network exhibits a higher glass transition temperature (), a higher tensile storage, and Young moduli than the corresponding UV-cured sample, indicating a lower elasticity and a shorter distance between the two adjacent crosslinking points. Above of Poly-TPGDA/LC blends, the LC behaves as a plasticizing agent, whereas, for EB-cured networks, at temperatures below , the LC shows a strong temperature dependence on the storage tensile modulus: the LC reinforces the polymer due to the presence of nano-sized phase separated glassy LC domains, confirmed by electron microscopy observations.

Systemically Administered TLR7/8 Agonist and Antigen-Conjugated Nanogels Govern Immune Responses against Tumors.

The generation of specific humoral and cellular immune responses plays a pivotal role in the development of effective vaccines against tumors. Especially the presence of antigen-specific, cytotoxic T cells influences the outcome of therapeutic cancer vaccinations. Different strategies, ranging from delivering antigen-encoding mRNAs to peptides or full antigens, are accessible but often suffer from insufficient immunogenicity and require immune-boosting adjuvants as well as carrier platforms to ensure stability and adequate retention.

Preparation of Monodisperse Giant Unilamellar Anchored Vesicles Using Micropatterned Hydrogel Substrates.

Giant unilamellar vesicles (GUVs) are model membrane systems consisting of a single lipid bilayer separating an inner lumen from the outer solution, with dimensions comparable to that of eukaryotic cells. The importance of these biomimetic systems has recently grown with the development of easy and safe methods to assemble GUVs from complex biorelevant compositions. However, size and position control is still a key challenge for GUV formation and manipulation.

Surfactants Mediate the Dewetting of Acrylic Polymer Films Commonly Applied to Works of Art.

The removal of hydrophobic polymer coatings from artistic surfaces is a ubiquitous challenge in art restoration. Over the years, nanostructured fluids (NSFs), aqueous surfactant solutions containing a good solvent for the polymer, have been successfully applied in polymer removal interventions; however, the precise role of the surfactant in promoting polymer film dewetting is not fully understood. This contribution addresses the interaction of a NSF of water/propylene carbonate containing a nonionic surfactant with an acrylic polymer film commonly used in art conservation.

Monitoring drug nanocarriers in human blood by near-infrared fluorescence correlation spectroscopy.

Nanocarrier-based drug delivery is a promising therapeutic approach that offers unique possibilities for the treatment of various diseases. However, inside the blood stream, nanocarriers' properties may change significantly due to interactions with proteins, aggregation, decomposition or premature loss of cargo. Thus, a method for precise, in situ characterization of drug nanocarriers in blood is needed.

Impact of Branching on the Solution Behavior and Serum Stability of Starlike Block Copolymers.

The size control of nanomedicines for tumor diagnosis and therapy is of high importance, since it enables or disables deep and sufficient tumor penetration. Amphiphilic star-shaped block copolypept(o)ides offer substantial promise to precisely adjust the hydrophobic core and the hydrophilic corona, independent of each other, and therefore simultaneously control the size dimension in the interesting size range from 10 to 30 nm. To gain access to core-shell structures of such sizes, 3-arm and 6-arm PeptoStars, based on poly(γ- tert-butyloxycarbonyl-l-glutamate)- b-polysarcosine (pGlu(O tBu)- b-pSar), were prepared via controlled living ring-opening polymerization (ROP) of the corresponding N-carboxyanhydrides.

Adsorption and Crystallization of Particles at the Air-Water Interface Induced by Minute Amounts of Surfactant.

Controlling the organization of particles at liquid-gas interfaces usually relies on multiphasic preparations and external applied forces. Here, we show that micromolar amounts of a conventional cationic surfactant induce, in a single step, both adsorption and crystallization of various types of nanometer- to micrometer-sized anionic particles at the air-water interface, without any additional phase involved or external forces other than gravity. Contrary to conventional surfactant-induced particle adsorption through neutralization and hydrophobization at a surfactant concentration close to the critical micellar concentration (CMC), we show that in our explored concentration regime (CMC/1000-CMC/100), particles adsorb with a low contact angle and maintain most of their charge, leading to the formation of two-dimensional assemblies with different structures, depending on surfactant ( C) and particle ( C) concentrations.

FRET Monitoring of Intracellular Ketal Hydrolysis in Synthetic Nanoparticles.

Degradable synthetic crosslinking is a versatile strategy to harness nanomaterials against disassembly in a complex physiological medium prompted by dilution effects or competitive interaction. In particular, chemical bonds such as ketals that are stable at physiological conditions but are cleaved in response to disease-mediated or intracellular conditions (e.g.

Nanocarrier for Oral Peptide Delivery Produced by Polyelectrolyte Complexation in Nanoconfinement.

The hydrophilic peptide YY (PYY) is a promising hormone-based antiobesity drug. We present a new concept for the delivery of PYY from pH-responsive chitosan-based nanocarriers. To overcome the drawbacks while retaining the merits of the polyelectrolyte complex (PEC) method, we propose a one-pot approach for the encapsulation of a hydrophilic peptide drug in cross-linked PEC nanocarriers.

Ultralow-intensity near-infrared light induces drug delivery by upconverting nanoparticles.

Mesoporous silica coated upconverting nanoparticles are loaded with the anticancer drug doxorubicin and grafted with ruthenium complexes as photoactive molecular valves. Drug release was triggered by 974 nm light with 0.35 W cm(-2).

Monitoring the dynamics of phase separation in a polymer blend by confocal imaging and fluorescence correlation spectroscopy.

The phase separation of the polymer blend polystyrene/poly(methyl phenyl siloxane) (PS/PMPS) is studied in situ by laser scanning confocal microscopy (LSCM) and by fluorescence correlation spectroscopy (FCS) at macroscopic and microscopic length scales, respectively. It is shown for the first time that FCS when combined with LSCM can provide independent information on the local concentration within the phase-separated domains as well as the interfacial width.

DNA amplification via polymerase chain reaction inside miniemulsion droplets with subsequent poly(n-butylcyanoacrylate) shell formation and delivery of polymeric capsules into mammalian cells.

There is a growing interest in the development of stable nanocapsules that could deliver the bioactive compounds within the living organism, and to release them without causing any toxic effects. Here the miniemulsion droplets were first used as "nanoreactors" for the amplification of single-molecule dsDNA template (476 and 790 base pairs) through PCR. Afterwards, each droplet was surrounded with a biodegradable PBCA shell by interfacial anionic polymerization, enabling therefore to deliver the PCR products into the cells.

Note: An easy way to enable total internal reflection-fluorescence correlation spectroscopy (TIR-FCS) by combining commercial devices for FCS and TIR microscopy.

Total internal reflection-fluorescence correlation spectroscopy (TIR-FCS) is a powerful method for studying dynamic processes at liquid-solid interfaces that may have numerous applications in biology, physics, and material science. Despite of its power and versatility, however, the use of TIR-FCS is still rather limited. The main reason for this is the need of a complex, in-house constructed optical setup whose assembly and adjustment is a quite difficult task.

Three-dimensional ferroelectric domain visualization by Cerenkov-type second harmonic generation.

We show that focusing a laser light onto the boundary between antiparallel ferroelectric domains leads to the non-collinear generation of two second harmonic (SH) beams. The beams are emitted in a plane normal to the domain boundaries at the angles that satisfy the Cerenkov-type phase matching condition. Moreover, these beam disappear when the laser light is focused on a homogenous part of a single domain.

Direct studies of liquid flows near solid surfaces by total internal reflection fluorescence cross-correlation spectroscopy.

We present a new method to study flow of liquids near solid surface: Total internal reflection fluorescence cross-correlation spectroscopy (TIR-FCCS). Fluorescent tracers flowing with the liquid are excited by evanescent light, produced by epi-illumination through the periphery of a high numerical aperture oil-immersion objective. The time-resolved fluorescence intensity signals from two laterally shifted observation volumes, created by two confocal pinholes are independently measured.

Direct measurements of hydrophobic slippage using double-focus fluorescence cross-correlation.

We report the results of direct measurements of velocity profiles in a microchannel with hydrophobic and hydrophilic walls, using a new high-precision method of double-focus spatial fluorescence cross correlation under a confocal microscope. In the vicinity of both walls the measured velocity profiles do not go to zero by supplying a plateau of constant velocity. This apparent slip is proven to be due to a Taylor dispersion, an augmentation by shear diffusion of nanotracers in the direction of flow.

Diffusion in polymer solutions studied by fluorescence correlation spectroscopy.

We employed fluorescence correlation spectroscopy (FCS) to study the diffusion of molecular and macromolecular tracers in polystyrene solutions over a broad range of concentrations (c) and molecular weights (M(w,m)) of the matrix polymer. Molecular tracer diffusion scales only with the matrix concentration and superimposes on a single, nonpolymer specific, curve. On the contrary, the diffusion of macromolecular tracers in solutions of matrix polymers with M(w,m) sufficiently larger than the tracer molecular weight scales with c/c(p)*, where c(p)* is the tracer overlap concentration.

Effect of capillary pressure and surface tension on the deformation of elastic surfaces by sessile liquid microdrops: an experimental investigation.

Sessile liquid drops are predicted to deform an elastic surface onto which they are placed because of the combined action of the liquid surface tension at the periphery of the drop and the capillary pressure inside the drop. Here, we show for the first time the in situ experimental confirmation of the effect of capillary pressure on this deformation. We demonstrate micrometer-scale deformations made possible by using a low Young's modulus material as an elastic surface.

Arrays of microlenses with variable focal lengths fabricated by restructuring polymer surfaces with an ink-jet device.

We report of a method for fabricating two-dimensional, regular arrays of polymer microlenses with focal lengths variable between 0.2 and 4.5 mm.

Impact of micropatterned surfaces on neuronal polarity.

Experimental control over cellular polarity in a neuronal network is a promising tool to study synapse formation and network behavior. We aimed to exploit a mechanism described by Stenger et al. [J.