Azopyridine : a smart photo- and chemo-responsive substituent for polymers and supramolecular assemblies

Azo dyes, such as azobenzene, are able to convert absorbed light into motion or deformation on the macroscopic scale on the basis of their remarkable ability to undergo repeatedly and in 100% yield reversibletrans-to-cisphotoisomerization. Current needs for multiresponsive and fast photoswitches have led to the development of heteroaryl azo dyes, such as azopyridine. This remarkable azo compound combines the photoresponse of the azo chromophore with the chemistry of the pyridine ring, in particular its responsiveness to changes in pH and its ability to form hydrogen- and halogen-bonds. This mini-review summarizes key features of the photoisomerization of polymer-tethered azopyridine in aqueous media and describes a few recent research accomplishments in emerging areas that have benefited of the fast thermalcis-to-transrelaxation characteristics of azopyridinium or H-bonded azopyridine. It also discusses the effects of the photoisomerization of azopyridine on the thermoresponsive properties of azopyridine-tethered heat-sensitive polymers. Overall, azopyridine is a highly versatile actuator to consider when designing photo/multiresponsive polymeric materials.Peer reviewe

Phototropic Multiresponsive Active Nanogels

Aqueous dispersions of nanogels that respond to switches in environmental pH and/or temperature by changes in their hydrodynamic radius (R-h) and/or zeta-potential are prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization-induced thermal (70 degrees C) self-assembly (PITSA) of N-isopropylacrylamide (NIPAM) in the presence of a poly(methacrylic acid) (PMAA)-substituted macromolecular chain transfer agent and a cross-linker. Photochromic spiropyran (SP) moieties are coupled to the carboxylic acid groups of the nanogels. Upon UV irradiation, the neutral SP isomerizes to the zwitterionic merocyanine (ME) form. Upon UV light irradiation, microgels formed by assembly of SP nanogels undergo a collective motion toward the UV-light source.Peer reviewe

Transition-Metal-Doped NIR-Emitting Silicon Nanocrystals

Impurity-doping in nanocrystals significantly affects their electronic properties and diversifies their applications. Herein, we report the synthesis of transition metal (Mn, Ni, Co, Cu)-doped oleophilic silicon nanocrystals (SiNCs) through hydrolysis/polymerization of triethoxysilane with acidic aqueous metal salt solutions, followed by thermal disproportionation of the resulting gel into a doped-Si/SiO2 composite that, upon HF etching and hydrosilylation with 1-n-octadecene, produces free-standing octadecyl-capped doped SiNCs (diameter approximate to 3 to 8 nm; dopant <0.2 atom %). Metal-doping triggers a red-shift of the SiNC photoluminescence (PL) of up to 270 nm, while maintaining high PL quantum yield (26% for Co doping).Peer reviewe

Nanostickers for cells : a model study using cell-nanoparticle hybrid aggregates

We present direct evidence that nanoparticles (NPs) can stick together cells that are inherently non-adhesive. Using cadherin-depleted S180 murine cells lines, which exhibit very low cell-cell adhesion, we show that NPs can assemble dispersed single cells into large cohesive aggregates. The dynamics of aggregation, which is controlled by diffusion and collision, can be described as a second-order kinetic law characterized by a rate of collision that depends on the size, concentration, and surface chemistry of the NPs. We model the cell-cell adhesion induced by the "nanostickers'' using a three-state dynamical model, where the NPs are free, adsorbed on the cell membrane or internalized by the cells. We define a "sticking efficiency parameter'' to compare NPs and look for the most efficient type of NP. We find that 20 nm carboxylated polystyrene NPs are more efficient nanostickers than 20 nm silica NPs which were reported to induce fast wound healing and to glue soft tissues. Nanostickers, by increasing the cohesion of tissues and tumors, may have important applications for tissue engineering and cancer treatment.Peer reviewe

How gluttonous cell aggregates clear substrates coated with microparticles

We study the spreading of cell aggregates deposited on adhesive substrates decorated with microparticles (MPs). A cell monolayer expands around the aggregate. The cells on the periphery of the monolayer take up the MPs, clearing the substrate as they progress and forming an aureole of cells filled with MPs. We study the dynamics of spreading and determine the width of the aureole and the level of MP internalization in cells as a function of MP size, composition, and density. From the radius and width of the aureole, we quantify the volume fraction of MPs within the cell, which leads to an easy, fast, and inexpensive measurement of the cell - particle internalization.Peer reviewe

Dehydration, Micellization, and Phase Separation of Thermosensitive Polyoxazoline Star Block Copolymers in Aqueous Solution

Suitably end-functionalized diblock copolymers (2-isopropyl-2oxazoline)-b-(2-ethyl-2-oxazoline) (PIPOZ-b-PEOZ) were linked to a tetrafunctional core to synthesize two isomeric thermosensitive 4-arm star block polymers which have the PIPOZ block near the core, core-(PIPOZ-bPEOZ)(4), or near the outer surface the star polymer, core-(PEOZ-b-PIPOZ)(4) The solution properties of the star copolymers in water were monitored by turbidimetry, microcalorimetry, and small-angle X-ray scattering (SAXS). The dehydration and cloud-point temperatures of both core-(PIPOZ-b-PEOZ)(4) and core-(PEOZ-b-PIPOZ)(4) in water are in the vicinity of 50 degrees C. Above this temperature, core-(PIPOZ-b-PEOZ)(4) forms starlike aggregates or star micelle, whereas core-(PEOZ-b-PIPOZ)(4) remains isolated, with no sign of aggregation. These results demonstrate the importance of chain architecture on the association of thermosensitive tetra-arm star block copolymers in water above the dehydration temperature.Peer reviewe

Spreading of Cell Aggregates on Zwitterion-Modified Chitosan Films

The sulfobetaine (SB) moiety, which comprises a quaternary ammonium group linked to a negatively charged sulfonate ester, is known to impart nonfouling properties to interfaces coated with polysulfobetaines or grafted with SB-polymeric brushes. Increasingly, evidence emerges that the SB group is, overall, a better antifouling group than the phosphorylcholine (PC) moiety extensively used in the past. We report here the synthesis of a series of SB-modified chitosans (CH-SB) carrying between 20 and 40 mol % SB per monosaccharide unit. Chitosan (CH) itself is a naturally derived copolymer of glucosamine and N-acetyl-glucosamine linked with a beta-1,4 bond. Analysis by quartz crystal microbalance with dissipation (QCM-D) indicates that CH-SB films (thickness similar to 20 nm) resist adsorption of bovine serum albumin (BSA) with increasing efficiency as the SB content of the polymer augments (surface coverage similar to 15 mu g cm(-2) for films of CH with 40 mol % SB). The cell adhesivity of CH-SB films coated on glass was assessed by determining the spreading dynamics of CT26 cell aggregates. When placed on chitosan films, known to be cell-adhesive, the CT26 cell aggregates spread by forming a cell monolayer around them. The spreading of CT26 cell aggregates on zwitterion-modified chitosans films is thwarted remarkably. In the cases of CH-SB30 and CH-SB40 films, only a few isolated cells escape from the aggregates. The extent of aggregate spreading, quantified based on the theory of liquid wetting, provides a simple in vitro assay of the nonfouling properties of substrates toward specific cell lines. This assay can be adopted to test and compare the fouling characteristics of substrates very different from the chemical viewpoint.Peer reviewe

Encapsulation and Delivery of Neutrophic Proteins and Hydrophobic Agents Using PMOXA-PDMS-PMOXA Triblock Polymersomes

Published under an ACS AuthorChoice LicensePolymersomes are attractive nanocarriers for hydrophilic and lipophilic drugs; they are more stable than liposomes, tunable, and relatively easy to prepare. The copolymer composition and molar mass are critical features that determine the physicochemical properties of the polymersomes including the rate of drug release. We used the triblockcopolymer, poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PIVIOXA-PDIVIS-PMOXA), to form amphipathic polymersomes capable of loading proteins and small hydrophobic agents. The selected agents were unstable neurotrophins (nerve growth factor and brain -derived neurotrophic factor), a large protein CD109, and the fluorescent drug curcumin. We prepared, characterized, and tested polymersomes loaded with selected agents in 2D and 3D biological models. Curcumin-loaded and rhodamine-bound PMOXA-PDMS-PMOXA polymersomes were used to visualize them inside cells. NMethyl-D-aspartate receptor (NNIDAR) agonists and antagonists were also covalently attached to the surface of polymersomes for targeting neurons. Labeled and unlabeled polymersomes with or without loaded agents were characterized using dynamic light scattering (DLS), UV-vis fluorescence spectroscopy, and asymmetrical flow field-flow fractionation (AF(4)). Polymersomes were imaged and tested for biological activity in human and murine fibroblasts, murine macrophages, primary murine dorsal root ganglia, and murine hippocampal cultures. Polymersomes were rapidly internalized and there was a clear intracellular co-localization of the fluorescent drug (curcumin) with the fluorescent rhodamine-labeled polymersomes. Polymersomes containing CD109, a glycosylphosphatidylinositol-anchored protein, promoted cell migration in the model of wound healing. Nerve growth factor-loaded polymersomes effectively enhanced neurite outgrowth in dissociated and explanted dorsal root ganglia. Brain -derived neurotrophic factor increased dendritic spine density in serum-deprived hippocampal slice cultures. NMDAR agonist-and antagomst-functionalized polymersomes targeted selectively neurons over filial cells in mixed cultures. Collectively, the study reveals the successful incorporation into polymersomes of biologically active trophic factors and small hydrophilic agents that retain their biological activity in vitro, as demonstrated in selected central and peripheral tissue models.Peer reviewe

Inert-living matter, when cells and beads play together

While both active and granular matter have been extensively studied, here we investigate what happens when we mix the two of them, in a model system combining microparticles and cell assemblies. On a substrate covered with polystyrene or silica microparticles, we notice two regimes in the spreading of a cell aggregate: light particles are pushed by the cells and form a ring, which bonds to the substrate by adhesion forces that oppose spreading, while for heavy particles, the cell monolayer spreads above the particle bed. In both cases, cell activity is transmitted to inert beads, leading to the formation of cell-microparticle aggregates, which flicker and diffuse. We then study the formation and the spreading of hybrid aggregates of microparticles and living cells and observe phase separations and jamming transitions. Our study may have implications on processes such as cancer metastasis and development, and may guide cancer therapies based on inert particles. Interaction of active matter with geometrical and topological constraints is a topic of intense research in the recent few years due to its potential for design and control of active flow patterns. Here, the authors experimentally study the growth and expansion of cell aggregates interleaved by passive colloidal particles, showing that inert particles can reshape the collective pattern formation in cellular aggregates.Peer reviewe

The Two Phase Transitions of Hydrophobically End-Capped Poly(N-isopropylacrylamide)s in Water

High-sensitivity differential scanning calorimetry (HS-DSC) thermograms of aqueous poly(N-isopropylacrylamide) (PNIPAM) solutions present a sharp unimodal endotherm that signals the heat-induced dehydration/collapse of the PNIPAM chain. Similarly, alpha,omega-di-n-octadecyl-PNIPAM (C18-PN-C18) aqueous solutions exhibit a unimodal endotherm. In contrast, aqueous solutions of alpha,omega-hydrophobically modified PNIPAMs with polycyclic terminal groups, such as pyrenylbutyl (Py-PN-Py), adamantylethyl (Ad-PN-Ad), and azopyridine- (C12-PN-AzPy) moieties, exhibit bimodal thermograms. The origin of the two transitions was probed using microcalorimetry measurements, turbidity tests, variable temperature H-1 NMR (VT-NMR) spectroscopy, and 2-dimensional NOESY experiments with solutions of polymers of molar mass (M-n) from 5 to 20 kDa and polymer concentrations of 0.1 to 3.0 mg/mL. The analysis outcome led us to conclude that the difference of the thermograms reflects the distinct self-assembly structures of the polymers. C18-PN-C18 assembles in water in the form of flower micelles held together by a core of tightly packed n-C18 chains. In contrast, polymers end-tagged with azopyridine, pyrenylbutyl, or adamantylethyl form a loose core that allows chain ends to escape from the micelles, to reinsert in them, or to dangle in surrounding water. The predominant low temperature (T-1) endotherm, which is insensitive to polymer concentration, corresponds to the dehydration/collapse of PNIPAM chains within the micelles, while the higher temperature (T-2) endotherm is attributed to the dehydration of dangling chains and intermicellar bridges. This study of the two phase transitions of telechelic PNIPAM homopolymer highlights the rich variety of morphologies attainable via responsive hydrophobically modified aqueous polymers and may open the way to a variety of practical applications.Peer reviewe