Release and Transport of Nanomaterials from Hydrogels Controlled by Temperature.

Understanding the transport of nanoparticles from and within hydrogels is a key issue for the design of nanocomposite hydrogels for drug delivery systems and tissue engineering. To investigate the translocation of nanocarriers from and within hydrogel networks triggered by changes of temperature, ultrasmall (8 nm) and small (80 nm) silica nanocapsules are embedded in temperature-responsive hydrogels and non-responsive hydrogels. The ultrasmall silica nanocapsules are released from temperature-responsive hydrogels to water or transported to other hydrogels upon direct activation by heating or indirect activation by Joule heating; while, they are not released from non-responsive hydrogel. Programmable transport of nanocarriers from and in hydrogels provides insights for the development of complex biomedical devices and soft robotics.

Organocatalytic Polymers from Affordable and Readily Available Building Blocks for the Cycloaddition of CO2 to Epoxides.

The catalytic cycloaddition of CO2 to epoxides to afford cyclic carbonates as useful monomers, intermediates, solvents, and additives is a continuously growing field of investigation as a way to carry out the atom-economic conversion of CO2 to value-added products. Metal-free organocatalytic compounds are attractive systems among various catalysts for such transformations because they are inexpensive, nontoxic, and readily available. Herein, we highlight and discuss key advances in the development of polymer-based organocatalytic materials that match these requirements of affordability and availability by considering their synthetic routes, the monomers, and the supports employed. The discussion is organized according to the number (monofunctional versus bifunctional materials) and type of catalytically active moieties, including both halide-based and halide-free systems. Two general synthetic approaches are identified based on the postsynthetic functionalization of polymeric supports or the copolymerization of monomers bearing catalytically active moieties. After a review of the material syntheses and catalytic activities, the chemical and structural features affecting catalytic performance are discussed. Based on such analysis, some strategies for the future design of affordable and readily available polymer-based organocatalysts with enhanced catalytic activity under mild conditions are considered.

Fast-release kinetics of a pH-responsive polymer detected by dynamic contact angles.

Polymers conjugated with active agents have applications in biomedicine, anticorrosion, and smart agriculture. When the active agent is used as a drug, corrosion inhibitor, or pesticide, it can be released upon a specific stimulus. The efficiency and the sustainability of active agents are determined by the released kinetics. In this work, we study the fast-release kinetics of 8-hydroxyquinoline (8HQ) from a pH-responsive, random copolymer of methyl methacrylate and 8-quinolinyl-sulfide-ethyl acrylate [P(MMA-co-HQSEA)] by hydrolysis of the ß-thiopropionate groups. We used contact angle measurements of sliding drops as an elegant way to characterize the release kinetics. Based on the results gained from 1H nuclear magnetic resonance measurement, fluorescent intensity measurement, and velocity-dependent contact angle measurement, we found that both the hydrolysis rate and polymer conformation affect the release kinetics of 8HQ from a P(MMA-co-HQSEA) film. Polymer chains collapse and further suppress the release from the inner layer in acidic conditions, while polymer chains in a stretched condition further facilitate the release from the inner layer. As a result, the cumulative release rate of 8HQ is higher in the basic condition than in the acidic condition.

Advanced density-based methods for the characterization of materials, binding events, and kinetics.

Investigations of the densities of chemicals and materials bring valuable insights into the fundamental understanding of matter and processes. Recently, advanced density-based methods have been developed with wide measurement ranges (i.e. 0-23 g cm-3), high resolutions (i.e. 10-6 g cm-3), compatibility with different types of samples and the requirement of extremely low volumes of sample (as low as a single cell). Certain methods, such as magnetic levitation, are inexpensive, portable and user-friendly. Advanced density-based methods are, therefore, beneficially used to obtain absolute density values, composition of mixtures, characteristics of binding events, and kinetics of chemical and biological processes. Herein, the principles and applications of magnetic levitation, acoustic levitation, electrodynamic balance, aqueous multiphase systems, and suspended microchannel resonators for materials science are discussed.

Degradable polyprodrugs: design and therapeutic efficiency.

Prodrugs are developed to increase the therapeutic properties of drugs and reduce their side effects. Polyprodrugs emerged as highly efficient prodrugs produced by the polymerization of one or several drug monomers. Polyprodrugs can be gradually degraded to release therapeutic agents. The complete degradation of polyprodrugs is an important factor to guarantee the successful disposal of the drug delivery system from the body. The degradation of polyprodrugs and release rate of the drugs can be controlled by the type of covalent bonds linking the monomer drug units in the polymer structure. Therefore, various types of polyprodrugs have been developed based on polyesters, polyanhydrides, polycarbonates, polyurethanes, polyamides, polyketals, polymetallodrugs, polyphosphazenes, and polyimines. Furthermore, the presence of stimuli-responsive groups, such as redox-responsive linkages (disulfide, boronate ester, metal-complex, and oxalate), pH-responsive linkages (ester, imine, hydrazone, acetal, orthoester, P-O and P-N), light-responsive (metal-complex, o-nitrophenyl groups) and enzyme-responsive linkages (ester, peptides) allow for a selective degradation of the polymer backbone in targeted tumors. We envision that new strategies providing a more efficient synergistic therapy will be developed by combining polyprodrugs with gene delivery segments and targeting moieties.

Confining the Sol-Gel Reaction at the Water/Oil Interface: Creating Compartmentalized Enzymatic Nano-Organelles for Artificial Cells.

Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ encapsulating enzymes in aqueous-core silica nanocapsules. In order to confine the sol-gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi-permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme-carrying nanocapsules, as synthetic nano-organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules.

Temperature-Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma.

Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-free quantitative liquid chromatography-mass spectrometry that the nanoparticles are largely enriched with apolipoprotein J (clusterin) at 25 °C while they are enriched with apolipoprotein A1 and apolipoprotein E at 37 °C. The temperature-dependent protein binding is found to significantly influence the uptake of the nanoparticles by RAW264.7 and HeLa cells. The findings imply that the functionalization of nanoparticles with temperature-responsive materials is a suitable method for imparting stealth properties to nanocarriers for drug-delivery.

Transparent and Self-Healing Elastomers for Reconfigurable 3D Materials.

Transparent soft materials are widely used in applications ranging from packaging to flexible displays, wearable devices, and optical lenses. Nevertheless, soft materials are susceptible to mechanical damage, leading to functional failure and premature disposal. Herein, a transparent self-healing elastomer that is able to repair the polymer network via exchange reactions of dynamic disulfide bonds is introduced. Due to its self-healing ability, the mechanical properties of the elastomer can be recovered as well as its transparency after multiple cycles of abrasion and healing. The self-healing polymer is fabricated into 3D structures by folding or modular origami assembly of planar self-healing polymer sheets. The 3D polymer objects are employed as storage containers of solid and liquid substances, reactors for photopolymerization, and cuvettes for optical measurements (exhibiting superior properties to those of commercial cuvettes). These dynamic polymers show outstanding mechanical, optical, and recycling properties that could potentially be further adapted in adaptive smart packaging, reconfigurable materials, optical devices, and recycling of elastomers.

Halochromic Polymer Nanosensors for Simple Visual Detection of Local pH in Coatings.

Replacing metallic structures before critical damage is beneficial for safety and for saving energy and resources. One simple approach consists in visually monitoring the early stage of corrosion, and related change of pH, of coated metals. We prepare smart nanoparticle additives for coatings which act as a pH sensor. The nanoparticles are formed with a terpolymer containing two dyes as side chains, acting as donor and acceptor for a FRET process. Real time monitoring of the extent of localized corrosion on metallic structures is then carried out with a smartphone camera. Colored pH mapping can be then manually retrieved by an operator or automatically recorded by a surveillance camera.

Brush Conformation of Polyethylene Glycol Determines the Stealth Effect of Nanocarriers in the Low Protein Adsorption Regime.

For nanocarriers with low protein affinity, we show that the interaction of nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin nanocarriers by dendritic cells using densely packed PEG chains with a "brush" conformation instead of the collapsed "mushroom" conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the nanocarriers. The brush conformation of PEG leads to a stealth behavior of the nanocarriers with inhibited uptake by phagocytic cells, which is a prerequisite for successful in vivo translation of nanomedicine to achieve long blood circulation and targeted delivery. We can clearly correlate the brush conformation of PEG with inhibited phagocytic uptake of the nanocarriers. This study shows that, in addition to the surface's chemistry, the conformation of polymers controls cellular interactions of the nanocarriers.

Ultrasmall Nanocapsules Obtained by Controlling Ostwald Ripening.

We describe here a method to synthesize ultrasmall nanocapsules with a diameter of 6 nm, exhibiting a well-defined core-shell morphology. Remarkably, the nanocapules are synthesized in a miniemulsion process without the need of large amounts of surfactant as commonly used in the microemulsion process. Ultrasmall nanocapsules with an oil core and a silica shell are formed by the concurrent processes of a sol-gel reaction and Ostwald ripening. Using solvents with different water solubilities and alkoxysilanes with different reactivities, we demonstrate that sizes of obtained nanocapsules depend on the ripening rate and alkoxysilane conversion rate. The method can be also used for encapsulating natural oils such as peppermint oil and limonene. This work shows that the Ostwald ripening phenomenon can be employed beneficially for the preparation of very small colloids.

From In Silico to Experimental Validation: Tailoring Peptide Substrates for a Serine Protease.

Smart nanocarriers for the transport of drugs to tumor cells are nowadays of great interest for treating cancer. The use of enzymatic stimuli to cleave peptide-based drug nanocapsules for the selective release of nanocapsule cargo in close proximity to tumor cells opens new possibilities in cancer research. In the present work, we demonstrate a methodology for finding and optimizing cleavable substrate sequences by the type II transmembrane serine protease hepsin, which is highly overexpressed in prostate cancer. The design and screening of combinatorial libraries in silico against the binding cavity of hepsin allow the identification of a panel of promising substrates with high-calculated docking scores. In vitro screening verifies the predictions and showed that all substrates are cleaved by hepsin with higher efficiency than the literature known hepsin substrate RQLR↓VVGG. The introduction of d-amino acids on a selected peptide with the highest catalytic efficiency (kcat/Km) renders it resistant to cleavage by plasma or serum while maintaining their susceptibility to hepsin.

Designing Smart Polymer Conjugates for Controlled Release of Payloads.

Incorporating labile bonds inside polymer backbone and side chains yields interesting polymer materials that are responsive to change of environmental stimuli. Drugs can be conjugated to various polymers through different conjugation linkages and spacers. One of the key factors influencing the release profile of conjugated drugs is the hydrolytic stability of the conjugated linkage. Generally, the hydrolysis of acid-labile linkages, including acetal, imine, hydrazone, and to some extent ß-thiopropionate, are relatively fast and the conjugated drug can be completely released in the range of several hours to a few days. The cleavage of ester linkages are usually slow, which is beneficial for continuous and prolonged release. Another key structural factor is the water solubility of polymer-drug conjugates. Generally, the release rate from highly water-soluble prodrugs is fast. In prodrugs with large hydrophobic segments, the hydrophobic drugs are usually located in the hydrophobic core of micelles and nanoparticles, which limits the access to the water, hence lowering significantly the hydrolysis rate. Finally, self-immolative polymers are also an intriguing new class of materials. New synthetic pathways are needed to overcome the fact that much of the small molecules produced upon degradation are not active molecules useful for biomedical applications.

Photocatalytic degradation of pesticides by nanofibrous membranes fabricated by colloid-electrospinning.

Photocatalytic degradation of organic pollutants is a promising way to clean wastewater. Herein, we develop and compare two processes for fabricating nanofibrous membranes with photocatalytic properties. Hybrid nanofibers are produced by colloid-electrospinning and composed of metal oxide nanoparticles on sintered SiO2 nanoparticles. The latter serves as support for the photocatalyst and preserves the structural integrity of nanofibers. Adsorption of metal salts on crosslinked polymer/SiO2 fibers followed by calcination allows for the obtention of fibers with large amounts of metal oxide. Nanofibrous membranes with supported ZnO, In2O3, or mixture of both, display photocatalytic activity upon UV irradiation. The membranes can degrade a dye and an organophosphate pesticide more effectively than membranes directly fabricated from the calcination of metal oxides.

Synergistic Anticancer Therapy by Ovalbumin Encapsulation-Enabled Tandem Reactive Oxygen Species Generation.

The anticancer efficacy of photodynamic therapy (PDT) is limited due to the hypoxic features of solid tumors. We report synergistic PDT/chemotherapy with integrated tandem Fenton reactions mediated by ovalbumin encapsulation for improved in vivo anticancer therapy via an enhanced reactive oxygen species (ROS) generation mechanism. O2.- produced by the PDT is converted to H2 O2 by superoxide dismutase, followed by the transformation of H2 O2 to the highly toxic . OH via Fenton reactions by Fe2+ originating from the dissolution of co-loaded Fe3 O4 nanoparticles. The PDT process further facilitates the endosomal/lysosomal escape of the active agents and enhances their intracellular delivery to the nucleus-even for drug-resistant cells. Cisplatin generates O2.- in the presence of nicotinamide adenine dinucleotide phosphate oxidase and thereby improves the treatment efficiency by serving as an additional O2.- source for production of . OH radicals. Improved anticancer efficiency is achieved under both hypoxic and normoxic conditions.

Regulating Payload Release from Hybrid Nanocapsules with Dual Silica/Polycaprolactone Shells.

We describe a facile strategy to synthesize hybrid nanocapsules with an oil core for hindering interactions between payloads and silica shell. Polycaprolactone/silica nanocapsules are synthesized by an interfacial sol-gel process occurring simultaneously with internal phase separation of the polymer produced by a miniemulsion-solvent evaporation technique. The localization of the polycaprolactone in the nanocapsules is depending on the ratio between polymer and silica. Formation of hybrid nanocapsules is found to significantly hinder interactions of drugs such as ibuprofen and carbamazepine with the silica surface.

Encapsulation and Release of Functional Nanodroplets Entrapped in Nanofibers.

A method is presented for preserving the structural integrity of nanodroplets produced by emulsification. Droplets of different hydrophobic liquids such as essential oils or monomers are produced by the miniemulsion process. The miniemulsions are then electrospun to yield dextran nanofibers entrapping the hydrophobic nanodroplets. The nanodroplets are then successfully redispersed by dissolving the nanofibers in water. Furthermore, it is shown that nanofibers can be used to store a monomer and a catalyst as healing agents for ring-opening metathesis polymerization. After dissolution, the healing agents are released and a self-healing reaction takes place. Embedding, storage, and release of emulsion nanodroplets is a promising method that avoids potential destabilization of droplets by coalescence or Ostwald ripening.

Encapsulation and Release of Essential Oils in Functional Silica Nanocontainers.

We describe the fabrication of mesoporous silica nanocontainers (SiO2NCs) that simultaneously encapsulate different antiseptic agents. Peppermint oil (PO), thyme oil (TO), cinnamon oil (CnO), and clove oil (CO), which are known to display antibacterial properties, are loaded in the core of the silica nanocontainers that are stabilized by antiseptic surfactants. The encapsulation efficiency, surface area, and pore size are controlled by the type of oil and surfactant. The release of essential oils is further controlled by grafting oxidized hyaluronic acid on silica nanocontainers functionalized with amino groups.

Redox-Responsive Polymer with Self-Immolative Linkers for the Release of Payloads.

Previous couplings of corrosion inhibitors to redox-responsive polymers via covalent bonding suffer from several drawbacks. It is presented here novel redox-responsive polymer-corrosion inhibitor conjugates that contain self-immolative linkers in their side chains. Very fast redox-induced release of tryptamine, a drug and a corrosion inhibitor, is observed after applying a reductive trigger.

Nanocontainers in and onto Nanofibers.

Hierarchical structure is a key feature explaining the superior properties of many materials in nature. Fibers usually serve in textiles, for structural reinforcement, or as support for other materials, whereas spherical micro- and nanoobjects can be either highly functional or also used as fillers to reinforce structure materials. Combining nanocontainers with fibers in one single object has been used to increase the functionality of fibers, for example, antibacterial and thermoregulation, when the advantageous properties given by the encapsulated materials inside the containers are transferred to the fibers. Herein we focus our discussion on how the hierarchical structure composed of nanocontainers in nanofibers yields materials displaying advantages of both types of materials and sometimes synergetical effects. Such materials can be produced by first carefully designing nanocontainers with defined morphology and chemistry and subsequently electrospinning them to fabricate nanofibers. This method, called colloid-electrospinning, allows for marrying the properties of nanocontainers and nanofibers. The obtained fibers could be successfully applied in different fields such as catalysis, optics, energy conversion and production, and biomedicine. The miniemulsion process is a convenient approach for the encapsulation of hydrophobic or hydrophilic payloads in nanocontainers. These nanocontainers can be embedded in fibers by the colloid-electrospinning technique. The combination of nanocontainers with nanofibers by colloid-electrospinning has several advantages. (1) The fiber matrix serves as support for the embedded nanocontainers. For example, through combining catalysts nanoparticles with fiber networks, the catalysts can be easily separated from the reaction media and handled visually. This combination is beneficial for the reuse of the catalyst and the purification of products. (2) Electrospun nanofibers containing nanocontainers offer the active agents inside the nanocontainers a double protection by both the fiber matrix and the nanocontainers. Since the polymer of the fibers and the polymer of the nanocontainers have usually opposite polarities, the encapsulated substance, for example, catalysts, dyes, or drugs, can be protected against a large variety of environmental influences. (3) Electrospun nanofibers exhibit unique advantages for tissue engineering and drug delivery that are a structural similarity to the extracellular matrix of biological tissues, large specific surface area, high and interconnected porosity which enhances cell adhesion, proliferation, drug loading, and mass transfer properties, as well as the flexibility in selecting the raw materials. Moreover, the nanocontainer-in-nanofiber structure allows multidrug loading and programmable release of each drug, which are very important to achieve synergistic effects in tissue engineering and disease therapy. The advantages offered by these materials encourage us to further understand the relationship between colloidal properties and fibers, to predict the morphology and properties of the fibers obtained by colloid-electrospinning, and to explore new possible combination of properties offered by nanoparticles and nanofibers.