Polymeric Nanoreactors Research Articles

Poly(N-vinylpyrrolidone)-Poly(dimethylsiloxane)-Based Polymersome Nanoreactors for Laccase-Catalyzed Biotransformations

Laccases (Lac) are oxidizing enzymes with a broad range of applications, for example, in soil remediation, as bleaching agent in the textile industry, and for cosmetics. Protecting the enzyme against degradation and inhibition is of great importance for many of these applications. Polymer vesicles (polymersomes) from poly(N-vinylpyrrolidone)-block-poly(dimethylsiloxane)-block-poly(N-vinylpyrrolidone) (PNVP-b-PDMS-b-PNVP) triblock copolymers were prepared and investigated as intrinsically semipermeable nanoreactors for Lac. The block copolymers allow oxygen to enter and reactive oxygen species (ROS) to leave the polymersomes. EPR spectroscopy proved that Lac can generate ROS. They could diffuse out of the polymersome and oxidize an aromatic substrate outside the vesicles. Michaelis-Menten constants Km between 60 and 143 μM and turn over numbers kcat of 0.11 to 0.18 s(-1) were determined for Lac in the nanoreactors. The molecular weight and the PDMS-to-PNVP ratio of the block copolymers influenced these apparent Michaelis-Menten parameters. Encapsulation of Lac in the polymersomes significantly protected the enzyme against enzymatic degradation and against small inhibitors: proteinase K caused 90% less degradation and the inhibitor sodium azide did not affect the enzyme's activity. Therefore, these polymer nanoreactors are an effective means to stabilize laccase.

Palladium nanoparticles encapsulated in magnetically separable polymeric nanoreactors

We report the preparation of magnetically separable catalytic polymeric nanoreactors by simultaneous encapsulation of palladium and magnetite nanoparticles within polyurea nanocapsules. The new catalytic material is applied in aqueous hydrogenation reactions.

A general strategy for creating self-defending surfaces for controlled drug production for long periods of time.

Infections associated with bacterial adhesion and subsequent biofilm formation constitute a grave medical issue for which conventional antibiotic therapies remain ineffective. Here, we introduce a new strategy employing nanotechnology to create smart surfaces with self-defending properties that result in controlled drug production and controlled release for long periods of time. Self-defending surfaces on solid supports are prepared by immobilizing polymer nanoreactors containing an encapsulated biocatalyst that can convert non-antibiotic substrates to an abiotic drug. For medical applications and biosensing, the immobilization method must fulfill specific criteria, and these were achieved by an immobilization strategy based on Schiff base formation between aldehyde groups on the outer surface of nanoreactors and amino groups on the solid support surface, followed by reductive amination. The resulting self-defending surfaces allow control of drug production at a specific rate for a specific period of time by adding predetermined amounts of substrate to the outer medium, minimization of dosages and therefore systemic toxicity, and limitation of the immune response. Such self-defending surfaces producing drugs offer a versatile strategy for the development of smart surfaces with improved stability and efficacy (by changing the biocatalyst) to serve as biosensors, antifouling surfaces, or smart packages.

Self-switchable catalysis by a nature-inspired polymer nanoreactor containing Pt nanoparticles

The proposed nanoreactor was made of Pt nanoparticles and a unique polymer composite of PVI and PTFMA. The self-healing and dissociation of the PVI–PTFMA interaction regulated access to the encapsulated metal nanoparticles, thereby causing self-switchable catalytic ability.

Thermoresponsive Polymer-Supported l-Proline Micelle Catalysts for the Direct Asymmetric Aldol Reaction in Water.

l-Proline moieties bound to a thermoresponsive polymer nanoreactor efficiently directed the asymmetric aldol reaction in water with excellent yields and enantioselectivity (ee). The reactions were efficient at higher temperatures in direct contrast to the low yields and ee values found when the reaction was carried out in a DMF/water mixture due to the location of the l-proline moieties within the hydrophobic pocket inside the core of the nanoreactors. This ideal environment formed for catalysis allows control over the water content as well as enhancing interactions between the carboxylic acid of l-proline and the aldehyde substrate. The nanoreactors were disassembled to fully water-soluble polymers by lowering the temperature to below the lower critical solution temperature (LCST) of the polymer, resulting in precipitation of the product in near pure form. The product was isolated by centrifugation and the polymer/water solution reused in additional catalytic cycles by heating the polymer above its LCST and thus reforming the nanoreactors. Although a small decrease in yield after five cycles was observed, the selectivity (anti/syn ratio and ee) remained high.

Polymer nanoreactors shown to produce and release antibiotics locally

We designed and prepared nanoreactors based on a poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline (PMOXA-b-PDMS-b-PMOXA) amphiphilic triblock copolymer encapsulating the enzyme penicillin acylase for local and controlled production of antibiotics.

Light-responsive polymer nanoreactors: a source of reactive oxygen species on demand

Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that encapsulate photosensitizer-protein conjugates in polymer vesicles as a source of "on demand" reactive oxygen species. Vesicles made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self-assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light scattering and transmission electron microscopy indicated that the nanoreactors are stable over time. They serve a dual role: protecting the photosensitizer in the inner cavity and producing in situ reactive oxygen species (ROS) upon irradiation with appropriate electromagnetic radiation. Illumination with appropriate wavelength light allows us to switch on/off and to control the production of ROS. Because of the oxygen-permeable nature of the polymer membrane of vesicles, ROS escape into the environment around vesicles, as established by electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with the appropriate laser light, produces ROS that induce cell death in a precise area corresponding to the irradiation zone. These nanoreactors can be used in theranostic approaches because they can be detected via the fluorescent photosensitizer signal and simultaneously produce ROS efficiently "on demand".

Catalytic polymeric nanoreactors: more than a solid supported catalyst

Polymeric nanostructures can be synthesized where the catalytic motif is covalently attached within the core domain and protected from the environment by a polymeric shell. Such nanoreactors can be easily recycled, and have shown unique properties when catalyzing reactions under pseudohomogeneous conditions. Many examples of how these catalytic nanostructures can act as nanosized reaction vessels have been reported in the literature. This prospective will focus on the exclusive features observed for these catalytic systems and highlight their potential as enzyme mimics, as well as the importance of further studies to unveil their full potential.

Polymer Nanoreactors with Dual Functionality: Simultaneous Detoxification of Peroxynitrite and Oxygen Transport

The design of multifunctional systems is in focus today as a key strategy for coping with complex challenges in various domains that include chemistry, medicine, environmental sciences, and technology. Herein, we introduce protein-containing polymer nanoreactors with dual functionality: peroxynitrite degradation and oxygen transport. Vesicles made of poly-(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated hemoglobin (Hb), which serves as a model protein because of its dual function in oxygen transport and peroxynitrite degradation. By inserting channel proteins, the polymer membranes of vesicles permitted passage of various compounds that served for the assessment of in situ Hb activity. The requisite conformational changes in the protein structure and the change in oxidation states that took place within the confined space of the vesicle cavity demonstrated that Hb preserved its dual functionality: peroxynitrite degradation and oxygen transport. The functionality of our nanoreactor, combined with its simple procedure of production and extensive stability over several months, supports it as a promising system for further medical applications.

ChemInform Abstract: Protein—Polymer Nanoreactors for Medical Applications

AbstractReview: 264 refs.

Size‐Tunable Polymeric Nanoreactors for One‐Pot Synthesis and Encapsulation of Quantum Dots

Hydrophilic polymeric nanoparticles are synthesized through a Bergman cyclization- mediated intramolecular chain collapse of structurally well-defined linear polymers, and then used as size-tunable nanoreactors to fabricate and encapsulate quantum dots in a one-pot reaction. Crystalline quantum dots are formed in all of these nanoreactors and visualized by transmission electron microscopy. Smaller nanoreactors produce one quantum dot each while larger nanoreactors form a number, resulting in fluorescence quenching. By controlling the molecular weight of the linear polymer precursor, a variable number of nanocrystals are fabricated and assembled in a single nanoreactor.

Quenching effects of gold nanoparticles in nanocomposites formed in water-soluble conjugated polymer nanoreactors

In this paper we describe the first example of the in situ synthesis of gold nanoparticles (AuNPs) in the presence of a water-soluble conjugated polyfluorene (NPF) presenting pendent ammonium groups, with the polymer acting as an aqueous surfactant and providing fluorescent nanoreactors. Using this approach, we produced well-dispersed NPF-AuNP nanocomposites without the need for any additional reducing agents. The photoluminescence emission intensity of NPF-AuNP nanocomposite solution was quenched to a greater extent upon increasing the concentration of AuNPs, presumably through energy transfer or electron transfer from the fluorescent polymer to the metal nanoparticles. Through variations in the degrees of protonation and deprotonation of the amino groups of NPF at different values of pH, we found that the extent of quenching of AuNPs in NPF-AuNP nanocomposite solutions was directly related to the adsorption and desorption behavior of NPF on the metal surfaces. Transmission electron microscopy revealed that the greatest aggregation of AuNPs in the nanocomposite solution occurred at pH 3, suggesting that the ammonium groups (RNMe2 at pH 8.5; RNMe2H+ at pH 3) of the polymer side chains adsorbed onto the AuNP surfaces under these conditions. Distinct time-resolved fluorescence signals of the AuNP-quenched NPF polymers at different values of pH confirmed the interactions between these species.

From polymeric nanoreactors to artificial organelles

Polymeric capsules have emerged as suitable nanocontainers to perform biocatalytic reactions. Recent developments have made it possible to control membrane permeability. Furthermore, their architecture allows the encapsulation of multiple enzymatic species, either in the same, or in different vesicular compartments to create nanoreactors capable of performing cascade reactions. Finally, by adding surface functionalities for cellular targeting and uptake, these polymeric nanoreactors can be taken up by cells, in which they effectively display their catalytic activity. Here we review recent advances made in the field of polymeric nanoreactors and their development towards artificial organelles for cellular applications.

Molecular recognition driven catalysis using polymeric nanoreactors

The concept of using polymeric micelles to catalyze organic reactions in water is presented and compared to surfactant based micelles in the context of molecular recognition. We report for the first time enzyme-like specific catalysis by tethering the catalyst in the well-defined hydrophobic core of a polymeric micelle.

Aldol reactions catalyzed by l-proline functionalized polymeric nanoreactors in water

The use of functional core-shell micelles as asymmetric catalytic nanoreactors for organic reactions in water is presented. An unprecedented increase in rate of reaction was achieved, which is proposed to be associated with the ability of the nanostructures to effectively concentrate the reagents in the catalytically active micelle core.

Protein–polymer nanoreactors for medical applications

Major challenges that confront nanoscience in medicine today include the development of efficacious therapies with minimum side effects, diagnostic methods featuring significantly higher sensitivities and selectivities, and personalized diagnostics and therapeutics for theragnostic approaches. With these goals in mind, combining biological molecules and synthetic carriers/templates, such as polymer supramolecular assemblies, represents a very promising strategy. In this critical review, we present protein-polymer systems as reaction spaces at the nano-scale in which the enzymatic reactions take place inside polymer supramolecular assembly, at its interface with the environment or in a combination of both. The location of the protein(s) with respect to the polymer assembly generates a diversity of systems ranging from nanoreactors to active enzymatic polymer surfaces. We describe these both in terms of general modelling and addressing the specific conditions and requirements related to the medical domain. We will particularly present protein-polymer nanoreactors that provide protected spaces for enzymatic reactions. We also show how polymer supramolecular structures, such as micelles, capsules, dendrimers and vesicles, can accommodate sensitive biomolecules to mimic natural systems and functions, and to serve as avenues for new medical approaches. Even though not yet on the market, we will emphasize possible applications of protein-polymer systems that generate reaction nanospaces-as novel ways to advanced medicine (264 references).

A surprising system: polymeric nanoreactors containing a mimic with dual-enzyme activity

Reactive oxygen species have been implicated in various diseases, but attempts to find efficient antioxidant treatments for such conditions have met with only limited success. Here, we have developed an antioxidant nanoreactor by encapsulating a dual-enzyme mimic of superoxide dismutase and catalase, in polymeric nanovesicles and examined how this nanoreactor combats oxidative stress. The mimic (CuIIENZm) is encapsulated inside poly-(2-methyloxazoline)–poly-(dimethylsiloxane)–poly(2-methyloxazoline) polymer vesicles that feature membranes permeable to superoxide, enabling the enzyme mimic to act in situ. We ensured that the size and shape of polymeric vesicles were not changed during the encapsulation procedure by analysis with light scattering and transmission electron microscopy, and that the structural geometry of CuIIENZm was preserved, as demonstrated by electron paramagnetic resonance and UV-vis spectroscopy. Due to its bi-functionality, CuIIENZm detoxified both superoxide radicals and related H2O2. The intracellular localization of the nanoreactor in THP-1 cells was established using confocal laser scanning microscopy and flow cytometry. No evident toxicity was found using MTS and LDH assays. As CuIIENZm remained active inside the vesicles therefore, these CuIIENZm-containing nanoreactors exhibited efficient antioxidant activity in THP-1 cells. Development of this simple, robust antioxidant nanoreactor represents a new direction in efficiently fighting oxidative stress.

Polymeric nanoreactors for enzyme replacement therapy of MNGIE

Polymeric nanoreactors for enzyme replacement therapy of MNGIE

Kinetic characteristics of the photoreduction of benzophenone in solid polymers in the presence of 4-halophenols

Benzophenone photoreduction in the presence of 4-halophenols (RC6H4OH; R = Cl, Br, and I) in a polymer glass is studied in terms of steady-state and nanosecond laser photolysis. The experimental data on the kinetics of the decay of the ketone triplet state are treated using a polychronous kinetic model in the assumption that two concurrent processes (hydrogen atom abstraction from the polymer and from the phenol) occur. The proton transfer rate constants averaged over the distribution and the parameter n that characterizes the distribution width were determined. The value of kav for the halophenols is shown to be more than an order of magnitude higher. No heavy atom effect is observed. The reaction product composition is demonstrated to change upon addition of a halophenol. The photoreduction in glass polymers is controlled by hydrogen atom abstraction from the respective donor by triplet ketone molecules. The reaction occurs predominantly in a polymer cage, a kind of polymer nanoreactor.

XANES studies of the formation of Ag-nanoparticles in LbL deposited polyelectrolyte thin films

Layer-by-layer polyelectrolyte multilayer thin films, composed of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) were used as polymeric nanoreactors for the nucleation and growth of Ag-nanoparticles. The effects of precursor conditions like the pH on the corresponding size, distribution and fractional composition of the embedded silver were studied before, during and after reduction process by means of NaBH4. X-ray absorption near edge structure (XANES) investigations enabled to distinguish between metallic Ag in the particles, dissolved Ag+-ions and Ag+-ions coordinated with carboxylic acid groups via a metal-ion exchange mechanism. The detailed analysis of the X-ray data showed that fractional composition of the embedded silver is determined by the processing conditions of the multilayer assembly during the nucleation and growth of Ag-nanoparticle PAH/PAA multilayer films. When the unreduced Ag-loaded PAH/PAA samples were exposed to ambient light, small Ag particles were formed within the polyelectrolyte multilayer films by reduction due to UV exposure. The formation of Ag-nanoparticles was confirmed by means of TEM and the characteristic plasmon resonance absorption peak in the UV–Vis range.