Force-Induced Near-Infrared Chromism of Mechanophore-Linked Polymers.

A near-infrared (NIR) mechanophore was developed and incorporated into a poly(methyl acrylate) chain to showcase the first force-induced NIR chromism in polymeric materials. This mechanophore, based on benzo[1,3]oxazine (OX) fused with a heptamethine cyanine moiety, exhibited NIR mechanochromism in solution, thin-film, and bulk states. The mechanochemical activity was validated using UV-vis-NIR absorption/fluorescence spectroscopies, gel permeation chromatography (GPC), NMR, and DFT simulations. Our work demonstrates that NIR mechanochromic polymers have considerable potential in mechanical force sensing, damage detection, bioimaging, and biomechanics.

Glycolipid-Containing Nanoparticle Vaccine Engages Invariant NKT Cells to Enhance Humoral Protection against Systemic Bacterial Infection but Abrogates T-Independent Vaccine Responses.

CD4+ T cells enable the critical B cell humoral immune protection afforded by most effective vaccines. We and others have recently identified an alternative source of help for B cells in mice, invariant NK T (iNKT) cells. iNKT cells are innate glycolipid-specific T cells restricted to the nonpolymorphic Ag-presenting molecule CD1d. As such, iNKT cells respond to glycolipids equally well in all people, making them an appealing adjuvant for universal vaccines. We tested the potential for the iNKT glycolipid agonist, α-galactosylceramide (αGC), to serve as an adjuvant for a known human protective epitope by creating a nanoparticle that delivers αGC plus antigenic polysaccharides from Streptococcus pneumoniae αGC-embedded nanoparticles activate murine iNKT cells and B cells in vitro and in vivo, facilitate significant dose sparing, and avoid iNKT anergy. Nanoparticles containing αGC plus S. pneumoniae polysaccharides elicits robust IgM and IgG in vivo and protect mice against lethal systemic S. pneumoniae However, codelivery of αGC via nanoparticles actually eliminated Ab protection elicited by a T-independent S. pneumoniae vaccine. This is consistent with previous studies demonstrating iNKT cell help for B cells following acute activation, but negative regulation of B cells during chronic inflammation. αGC-containing nanoparticles represent a viable platform for broadly efficacious vaccines against deadly human pathogens, but their potential for eliminating B cells under certain conditions suggests further clarity on iNKT cell interactions with B cells is warranted.

Drug Delivery and Drug Efficacy from Amorphous Poly(thioether anhydrides).

The correlation between erosion and drug (lidocaine and 6-mercaptopurine, 6-MP) release from amorphous poly(thioether anhydrides), which are synthesized using radical-mediated thiol-ene polymerization, is reported. Cytotoxicity studies of the polymer toward human fibroblast human dermal fibroblasts adult, melanoma A-375, and breast cancer MCF-7 cells are conducted, and drug efficacy of a cancer and autoimmune disease drug (6-MP) when released from the poly(thioether anhydrides) is examined against two cancerous cell types (A-375 and MCF-7). Erosion and drug release studies reveal that lidocaine release is governed by network erosion whereas 6-MP is released by a combination of erosion and diffusion. The cytotoxicity studies show that all three cell types demonstrate high viability, thus cytocompatibility, to poly(thioether anhydrides). Toxicity to the material is dose dependent and comparable to other polyanhydride systems. The 6-MP cancer drug is shown to remain bioactive after encapsulation in the poly(thioether anhydride) matrix and the polymer does not appear to modify the efficacy of the drug.

Raman Microspectroscopy Study of the Hydrolytic Degradation of Polyanhydride Network Polymers.

Raman microspectroscopy was employed in this work to study the degradation of a polyanhydride network polymer synthesized from 4-pentenoic anhydride and pentaerythritol tetrakis(3-mercaptopropionate) monomers in order to illustrate the utility of this method and improve the understanding of the polyanhydride degradation and erosion. Disk-shaped polymer samples were immersed in buffer solutions for different periods of time, and hydrolytic degradation was monitored spatially and temporally via kinetic Raman studies at various depths of penetration into the samples. Erosion, meanwhile, was monitored via mass loss measurements. Dispersive Raman microspectroscopy is shown to be a particularly valuable tool for the study of the hydrolytic degradation of these materials. It confirms that these thiol-ene polyanhydrides are indeed surface eroding, while also revealing that degradation starts to occur at the core of samples on a short time scale (less than 5 h). At any given degradation time, there is a concentration gradient of the unreacted anhydride, with the unreacted anhydride concentration increasing from the outer edge to the center of the polymer samples. Further, the anhydride functionality is found to decrease approximately linearly with degradation time at all depths in the samples, though the degradation rate does appear to increase slightly as degradation occurs.

Quantitative and qualitative toxicological evaluation of thiol-ene "click" chemistry-based polyanhydrides and their degradation products.

Quantitative and qualitative toxicological analyses of crosslinked, surface-eroding polyanhydrides (PAHs) made from thiol-ene "click" polymerizations are reported. The cytotoxicity of these PAHs was investigated against three skin-based cell types; melanoma (A-375), human dermal fibroblast adult (HDFa), and 3T3-J2 (mouse fibroblast) cells, thus providing insight into the potential for these PAHs to be used in dermal drug delivery applications. Apoptosis was evaluated quantitatively and qualitatively using MTT assay and fluorescence microscopic imaging as indication of cytotoxicity. Upon exposure of A-375 and HDFa cells to high concentrations (4000 mg/L) of crosslinked PAH, the respective morphologies remained relatively unchanged compared with nonexposed cells. The 3T3-J2 cell type was more sensitive towards the PAH, exhibiting minimal deformation of cell morphology at 4000 mg/L. The MTT assay and fluorescence imaging revealed that this PAH and its degradation products are highly cytocompatible at high concentrations and cytotoxicity observed is dosage/time dependent. Further, the PAH did not induce inhibition of tested cells' proliferation at high polymer concentration up to 2000 mg/L. The IC50 (concentration of the crosslinked PAH required to inhibit 50% cell viability) for HDFa and A-375 cells was determined to be 4300 ± 70 and 8500 ± 50 mg/L, respectively. The high cytocompatibility of this type of crosslinked PAH, in addition to their degradation products, towards these skin cells (standard and cancer cell types) suggests that the polymer may be viable for dermal-based drug delivery to normal and cancerous diseased tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1936-1945, 2016.

Anhydride-Based Reconfigurable Shape Memory Elastomers.

Soft shape memory polymers typically embody a permanently memorized geometry that cannot be altered, and therefore a new sample must be fabricated each time a new structure is required. We present a shape memory elastomeric composite featuring thermoplastic fibers as a fixing phase and a polyanhydride-based elastomer as the permanent, elastic phase. Interestingly, dynamic covalent exchange reactions at elevated temperatures (T > 50 °C) among the network chains of the elastomer allow near-complete reconfiguration of the permanent shape in the solid state. Together, these features combine to create a shape memory elastomer capable of arbitrary programming of both temporary and permanent shapes.

Surface Eroding, Semicrystalline Polyanhydrides via Thiol-Ene "Click" Photopolymerization.

Surface eroding and semicrystalline polyanhydrides, with tunable erosion times and drug delivery pharmacokinetics largely dictated by erosion, are produced easily with thiol-ene "click" polymerization. This strategy yields both linear and cross-linked network polyanhydrides that are readily and fully cured within minutes using photoinitiation, can contain up to 60% crystallinity, and have tensile moduli up to 25 MPa for the compositions studied. Since they readily undergo hydrolysis and exhibit the oft-preferred surface erosion mechanism, they may be particularly useful in drug delivery applications. The polyanhydrides were degraded under pseudophysiological conditions and cylindrical samples (10 mm diameter × 5 mm height) were completely degraded within ∼10 days, with the mass-time profile being linear for much of this time after a ∼24 h induction period. Drug release studies, using lidocaine as a model, showed pharmacokinetics that displayed a muted burst release in the early stages of erosion, but then a delayed release profile that is closely correlated to the erosion kinetics. Furthermore, cytotoxicity studies of the linear and cross-linked semicrystalline polyanhydrides, and degradation products, against fibroblast cells indicate that the materials have good cytocompatibility. Overall, cells treated with up to 2500 mg/L of the semicrystalline polyanhydrides and degradation products show >90% human dermal fibroblast adult (HDFa) cell viability indicative of good cytocompatibility.

Reaction-diffusion degradation model for delayed erosion of cross-linked polyanhydride biomaterials.

We develop a theoretical model to explain the long induction interval of water intake that precedes the onset of erosion due to degradation caused by hydrolysis in the recently synthesized and studied cross-linked polyanhydrides. Various kinetic mechanisms are incorporated in the model in an attempt to explain the experimental data for the mass loss profile. Our key finding is that the observed long induction interval is attributable to the nonlinear dependence of the degradation rate constants on the local water concentration, which essentially amounts to the breakdown of the standard rate-equation approach, potential causes for which are then discussed. Our theoretical results offer physical insights into which microscopic studies will be required to supplement the presently available macroscopic mass-loss data in order to fully understand the origin of the observed behavior.

Bottlenecks in proteomics.

Mass spectrometry (MS) is the core for advanced methods in proteomic experiments. When effectively used, proteomics may provide extensive information about proteins and their post-translational modifications, as well as their interaction partners. However, there are also many problems that one can encounter during a proteomic experiment, including, but not limited to sample preparation, sample fractionation, sample analysis, data analysis & interpretation, and biological significance. Here we discuss some of the problems that researchers should be aware of when performing a proteomic experiment.

Photopolymerized cross-linked thiol-ene polyanhydrides: erosion, release, and toxicity studies.

Several critical aspects of cross-linked polyanhydrides made using thiol-ene polymerization are reported, in particular the erosion, release, and solution properties, along with their cytotoxicity toward fibroblast cells. The monomers used to synthesize these polyanhydrides were 4-pentenoic anhydride and pentaerythritol tetrakis(3-mercaptopropionate). Techniques used to evaluate the erosion mechanism indicate a complex situation in which several phenomena, such as hydrolysis rates, local pH, water diffusion, and solubility, may be influencing the erosion process. The mass loss profile, the release rate of a hydrophilic dye, the rate of hydrolysis of the polyanhydride, the hydrolysis product solubility as a function of pH, average pK(a) and its cytotoxicity toward fibroblast cells were all determined. The solubility of the degradation product is low at pH values less than 6-7, and the average pKa was determined to be ~5.3. The cytotoxicity of the polymer and the degradation product was found to be low, with cell viabilities of >97% for the various samples studied at concentrations of ~1000-1500 ppm. These important parameters help determine the potential of the thiol-ene polyanhydrides in various biomedical applications. These polyanhydrides can be used as a delivery vehicle, and although the release profile qualitatively followed the mass loss profile for a hydrophilic dye, the release rate appears to be by both diffusion and mass loss mechanisms.

Imprint lithography with degradable elastomeric polyanhydrides.

A photocurable, degradable polyanhydride cross-linked elastomer that can be used as a stamp in imprint lithography applications has been developed. The degradable stamp materials are based on polyanhydrides synthesized using thiol-ene polymerization. In this study, curing the monomers 4-pentenoic anhydride and pentaerythritol tetrakis(3-mercaptopropionate) on a master mold yields low modulus, elastomeric, degradable polyanhydride polymer stamps that are a negative of the master. These stamps can be then used as a sacrificial template during the fabrication of a replica of the master, and can be readily degraded away from the replica using water. The resultant imprinted materials exhibited excellent uniformity over a large area. Compared with other conventional imprint lithography stamp materials, the thiol-ene polymerized polyanhydrides are degradable, master mold safe, show great release properties, have fast cure rates, are relatively low cost, and can be fabricated onto variety of substrates and materials.

Recent developments in atom transfer radical polymerization (ATRP): methods to reduce metal catalyst concentrations.

Atom transfer radical polymerization (ATRP) was initially developed in the mid-1990s, and with continued refinement and use has led to significant discoveries in new materials. However, metal contamination of the polymer product is an issue that has proven detrimental to widespread industrial application of ATRP. The laboratories of K. Matyjaszewski have made significant progress towards removing this impediment, leading the development of "activators regenerated by electron transfer" ATRP (ARGET ATRP) and electrochemically mediated ATRP (eATRP) technologies. These variants of ATRP allow polymers to be produced with great molecular weight and functionality control but at significantly reduced catalyst concentrations, typically at parts per million levels. This Concept examines these polymerizations in terms of their mechanism and outcomes, and is aimed at giving the reader an overview of recent developments in the field of ATRP.

Polymer Microspheres Prepared by Water-Borne Thiol-Ene Suspension Photopolymerization.

Thiol-ene polymerizations are shown to be possible in a water-borne suspension-like photopolymerization and yield spherical particles that have diameters in the range of submicrometers to hundreds of micrometers. This is the first report of such colloidal thiol-ene polymerizations. Thiol-ene polymerization offers unique conditions not commonly associated with a water-borne polymerization including a step-growth polymerization mechanism along with photoinitiation under ambient conditions. Example polymerizations of a triene, 3,5-triallyl-1,3,5-triazine-2,4,6 (1N,3H,5H)-trione (TTT), and a tetrathiol, pentaerythritol tetrakis(3-mercaptopropionate) (PETMP), with the photoinitiator 1-hydroxycyclohexyl phenyl ketone, surfactant sodium dodecyl sulfate (SDS), and a cosolvent (chloroform or toluene) are discussed. Various experimental parameters were examined such as surfactant concentration, homogenization energy, cosolvent species, and cosolvent amount in order to develop an understanding of the mechanism of microsphere formation. It is demonstrated that particle size is dependent on homogenization energy, with greater mechanical shear yielding smaller particles. In addition, higher concentrations of surfactant or solvent also produced smaller spherical particles. These observations lead to the conclusion that the particles are formed via a suspension-like polymerization.

Mechanism of titania deposition into cylindrical poly(styrene-block-4 vinyl pyridine) block copolymer templates.

A simple and effective way for TiO(2) to be deposited on silicon or indium tin oxide (ITO) substrates has been achieved by using a poly(styrene-block-4-vinyl pyridine) (PS-b-P4VP) block copolymer template. In particular, a mechanism for the formation of TiO(2) within the P4VP phase was developed. Within this model, the TiO(2) deposition occurs by swelling of the protonated P4VP segments followed by transport of Ti precursor, probably protonated Ti(OH)(4) given the low pH conditions used, into the swollen P4VP followed by condensation into TiO(2) during the heating/plasma etch processes. TiO(2) nanostructure morphology is affected by pH and deposition temperatures, because these parameters affect the degree of protonation of P4VP segments and diffusion of the titanium(IV) bis(ammonium lactato)dihydroxide (TALH) precursor into the film. A pH range of 2.1-2.5 for silicon substrates and pH = 2.1 for ITO substrates gave the narrower TiO(2) nanostructures distributions, and deposition at 70 °C gave TiO(2) nanostructures with more regular arrangements and smoother surface than those deposited at room temperature. The use of 1,4-diiodobutane as a P4VP cross-linking compound is demonstrated to be a critical parameter for maintaining good cylindrical surface morphology for both the block copolymer template and the TiO(2) nanostructures.

Periodic titania nanostructures using block copolymer templates.

The deposition of periodic titania nanostructures, templated by a polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer, is reported. When cast as a thin film (30-50 nm thick), the PS-b-P4VP forms a morphology that consists of P4VP cylinders that are orientated perpendicular to the substrate. The P4VP phase was lightly cross-linked by exposing the film to diiodobutane. When the block copolymer film was exposed to the sol-gel titania precursor, titanium(IV) bis(ammonium lactate) dihydroxide (TALH), titania was formed in the P4VP phase. The resulting titania structures were identical in size to the P4VP cylinders and only formed (under the deposition conditions used in this study) when the block copolymer film was present on the substrate, thus providing evidence that the block copolymer indeed acts as a template. The process works for both silicon and indium tin oxide substrates.

Elastomeric and degradable polyanhydride network polymers by step-growth thiol-ene photopolymerization.

Linear and crosslinked polyanhydrides can be made using photoinitiated thiol-ene chemistry, a simple and effective method of making crosslinked structures that have surface degradation characteristics.

Structure and melt rheology of polystyrene-based layered silicate nanocomposites.

The melt-state viscoelastic properties of exfoliated in situ polymerized and intercalated solution-blended polystyrene (PS) and organically modified montmorillonite nanocomposites were investigated and compared. The PS nanocomposites prepared by nitroxide-mediated polymerization (NMP) exhibit a stable exfoliated structure whereas the PS nanocomposites prepared by solution mixing exhibit an intercalated structure. The linear viscoelastic properties were strongly correlated with the dispersion state of the nanocomposites. On the other hand, the non-linear oscillatory shear properties exhibited shear thinning character and were consistent with the weak interactions between the polymer and the layered silicate.