Enzyme responsive polymers applications

Enzyme-responsive polymers properties, synthesis and applications... 

Enzyme-responsive polymers stand apart from other stimuli-responsive polymers in their ability to respond to a biological molecule to regulate the function of natural materials. Ihis is both a strength and a limitation while enzyme-responsive polymers are uniquely suited to perform tasks in their niche area (i.e., in a biological surrounding), they cannot readily be used in other applications that do not preserve the activity of enzymes. 

Within their designed areas of application, however, the versatility of enzyme-responsive polymers is unmatched by any other stimuli-responsive materials. Enzyme-responsive polymers have found applications as cell supports, injectable scaffolds and drug delivery systems and have been integrated with other stimuli-responsive polymers to obtain materials with closely tailored stimuli-responsive characteristics. While research in the development of enzyme-responsive materials (ERMs) is still in its early... 

By nature, ERMs are inherently suitable for applications in the healthcare section. Despite being a young class of materials, some exciting applications have begun to emerge. Here, three applications for enzyme-responsive polymers are highlighted cell supports, injectable scaffolds and drug delivery devices. 

Enzyme-triggered release of bioactive molecules from a polymer based material is possibly the most intensely researched application for enzyme-responsive polymers. Such delivery systems typically employ vehicles such as micelles, solid particles and capsules to contain and protect a drug and deliver it to the site of action either by injection directly into the diseased tissue or by circulation through the blood stream. At the site of action, the enzyme will degrade the polymer, cause disassembly of the micelle or swell the particle and thus cause release of the drug into the environment. 

The predisposition of ERMs to be used as biomaterials comes with some limitations. As the material relies on enzymes as stimuli, the operating conditions must preserve the function of the enzyme. This typically restricts the use of enzyme-responsive polymers to applications that respond under these circumstances. Although several enzymes are known that operate outside these conditions (e.g., at elevated temperatures or in organic solvents), no stimuli-responsive materials have yet been developed that respond to these enzymes. Moreover, since the application of ERMs is focused on biological systems, the polymers used have to be biocompatible and be able to withstand the effects of a complex biological environment in which they have to maintain their function. 

Finally, the claim that enzyme-responsive polymers are highly suited for biomedical applications has been frequently justified by model studies including both in vitro and in vivo work (Jin et a/., 2010 Kurisawa et al., 2005). In order to truly exploit the potential of these materials, work that facilitates the translation of these materials into applications needs to be intensified. It is expected that the demand for a stronger drive towards the development of enzyme-responsive polymers into commercially viable materials will be recognised in the near future, and that we will see an increase in the effort to drive the research in this area forward. 

Acrylamide is the first bulk chemical manufactured using an industrial biotransformation. Acrylamide which is produced 200000 t/a is an important industrial chemical that is mainly processed into water-soluble polymers and copolymers, which find applications as flocculants, paper-making aids, thickening agents, surface coatings, and additives for enhanced oil recovery. The chemical manufacture of acrylamide has been established for a long time, it is based on Cu-catalysis. The production of acrylamide using immobilized whole cells of Rhodococcus rhodochrous is a remarkable example of a lyase-catalyzed commercial process. The enzyme responsible for water addition to the double bond of acrylonitrile is nitrile hydratase (Eq. 4-17) ... 

Stimuli-responsive polymers have gained increasing interest and served in a vast number of medical and/or pharmaceutical applications such as implants, medical devices or controlled drug delivery systems, enzyme immobilization, immune-diagnosis, sensors, sutures, adhesives, adsorbents, coatings, contact lenses, renal dialyzers, concentration and extraction of metals, for enhanced oil recovery, and other specialized systems (Chen and Hsu 1997 Chen et al. 1997 Wu and Zhou 1997 Yuk et al. 1997 Bayhan and Tuncel 1998 Tuncel 1999 Tuncel and Ozdemir 2000 Hoffman 2002 en and Sari 2005 Fong et al. 2009). Some novel applications in the biomedical field using stimuli-responsive materials in bulk or just at the surface are shape-memory (i.e., devices that can adapt shape to facilitate the implantation and recover their conformation within the body to... 

Responsive polymer bmshes are not only investigated on planar substrates, but can also be used to decorate nanoparticles (Figure 5.13). Here, the key biomedical application is the accommodation (immobilize) of biofunctional moieties such as proteins or enzymes (Wittemann Ballauff, 2006 Wittemann, Haupt, BaUauff, 2003). If there is sufficient attraction between a protein and a polymer brush to overcome excluded volume effects (the antifouling properties of the brush), much larger amounts of protein can accumulate inside a brnsh layer than can be adsorbed onto just the particles surface. The role of the attached polymer chains is thus to strongly increase the available surface area. In Fignre 5.13, we schematically show a spherical polymer brush filled with adsorbed nanoparticles. Because, protein molecules inunobilized by polymers are found to be relatively weakly bound, they keep their conformation and (enzymatic)... 

Key words enzyme-responsive materials (ERMs), regenerative medicine and drug delivery applications, polymer hydrogels and scaffolds, supramolecular particles and self-assembly polymer particles. 

Polymer hydrogels consist of a cross-finked network of hydrophilic polymers with a very large water content (up to 99%) (Wichterle and Lim, 1960).They are structurally similar to the ECM and have therefore frequently been used as ECM mimics (Fedorovich et al., 2007 Shoichet, 2010). Other biological applications include the use as injectable scaffolds, (temporary) cell culture supports and drug delivery matrices (Mano, 2008). For all these applications, the introduction of enzyme-responsive functionalities into the polymer hydrogel is attractive because it would either more closely mimic the ECM (which is itself enzyme responsive) or allow drug delivery in response to the presence of a specific enzyme. 

Characterisation of the enzyme-responsive material prepared through the methods outlined above is essential not only to test the enzyme responsiveness of the polymer but also to characterise the material s overall performance under the conditions in which it will be used in its ultimate application. This section will provide a brief overview of standard and specialised techniques that have been employed for this purpose and covers mechanical, chemical, physical and biological properties as well as enzyme responsiveness. While we will discuss the reason for choosing particular techniques and explain their advantages and Umitations in the context of the analysis of enzyme-responsive materials, explanations of the working principles of the techniques will not be provided and the reader is referred to other specialised textbooks on this topic instead. 

Over the past 5 years, a number of researchers have started to explore and mimic these approaches in the laboratory. Enzyme-assisted formation of supramolecular polymers has several unique features. These include selectivity, confinement and catalytic amplification, which allow for superior control as observed in biological systems. These systems are finding applications in areas where supramolecular function is directly dictated by molecular order, for example in designed biomaterials for 3D cell culture, templating, drug delivery, biosensing, and intracellular polymerisations to control cell fate. Overall, biocatalytic production of supramolecular polymers provides a powerful new paradigm in stimuli-responsive nanomaterials. 

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