Macromolecular Entities Research Articles

An in-silico approach to understand the potential role of Wnt inhibitory factor-1 (WIF-1) in the inhibition of the Wnt signalling pathway

WIF1 (Wnt inhibitory factor 1) is a potent tumour suppressor gene which is epigenetically silenced in numerous malignancies. The associations of WIF1 protein with the Wnt pathway molecules have not been fully explored, despite their involvement in the downregulation of several malignancies. In the present study, a computational approach encompassing the expression, gene ontology analysis and pathway analysis is employed to obtain an insight into the role of the WIF1 protein. Moreover, the interaction of the WIF1 domain with the Wnt pathway molecules was carried out to ascertain the tumour-suppressive role of the domain, along with the determination of their plausible interactions. Initially, the protein-protein interaction network analysis endowed us with the Wnt ligands (such as Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt8a and Wnt9a), along with the Frizzled receptors (Fzd1 and Fzd2) and the low-density lipoprotein complex (Lrp5/6) as the foremost interactors of the protein. Further, the expression analysis of the aforementioned genes and proteins was determined using The Cancer Genome Atlas to comprehend the significance of the signalling molecules in the major cancer subtypes. Moreover, the associations of the aforementioned macromolecular entities with the WIF1 domain were explored using the molecular docking studies, whereas the dynamics and stability of the assemblage were investigated using 100 ns molecular dynamics simulations. Therefore, providing us insights into the plausible roles of WIF1 in inhibiting the Wnt pathways in various malignancies. Communicated by Ramaswamy H. Sarma

Graft onto approaches for nanocellulose-based advanced functional materials.

The resurgence of cellulose as nano-dimensional 'nanocellulose' has unlocked a sustainable bioeconomy for the development of advanced functional biomaterials. Bestowed with multifunctional attributes, such as renewability and abundance of its source, biodegradability, biocompatibility, superior mechanical, optical, and rheological properties, tunable self-assembly and surface chemistry, nanocellulose presents exclusive opportunities for a wide range of novel applications. However, to alleviate its intrinsic hydrophilicity-related constraints surface functionalization is inevitably needed to foster various targeted applications. The abundant surface hydroxyl groups on nanocellulose offer opportunities for grafting small molecules or macromolecular entities using either a 'graft onto' or 'graft from' approach, resulting in materials with distinctive functionalities. Most of the reviews published to date extensively discussed 'graft from' modification approaches, however 'graft onto' approaches are not well discussed. Hence, this review aims to provide a comprehensive summary of 'graft onto' approaches. Furthermore, insight into some of the recently emerging applications of this grafted nanocellulose including advanced nanocomposite formulation, stimuli-responsive materials, bioimaging, sensing, biomedicine, packaging, and wastewater treatment has also been reviewed.

Double‐Sided Graphene‐Enhanced Raman Scattering and Fluorescence Quenching in Hybrid Biological Structures

AbstractDue to their large contact and loading surfaces as well as high sensitivities to chemical changes, graphene‐based materials (GBMs) are increasingly being employed into novel nanomedicine technologies. Here biomolecule—monolayer graphene—kidney tissue hybrid structures are studied using mapping micro‐Raman and fluorescence spectroscopies. Because in this configuration graphene interacts with molecules on both sides, a double‐sided graphene‐enhanced Raman scattering (GERS) effect up to ≈10.1 is found for biomolecules adsorbed on graphene and amino acids in the kidney tissue below graphene. Moreover, graphene causes an efficient autofluorescence quenching (FLQ) up to ≈20% emitted by the kidney tissue. Despite the complexity of such layered materials, the intriguing simultaneous occurrence of double‐sided GERS (a new development of GERS) and FLQ phenomena can be well explained by suitable molecular structure and energy level alignment between molecules and graphene. These result in effective charge transfer mediated by non‐covalent interactions as indicated by correlative strain, doping, and defect analyses in graphene based on the Raman data and energy level calculations. Last, the advantages of using graphene over standard photobleaching are demonstrated. This work can be extended to other macromolecular entities toward integrating GBMs in versatile drug delivery, imaging, and sensing devices.

On interactions in binary mixtures used in solvent extraction: Insights from combined Isothermal Titration Calorimetry experiments and Molecular Dynamics simulations

Despite its importance, the description of liquid–liquid extraction is made difficult because the link between the experimental methods and the interactions present in the solution is not direct due to the many organisation phenomena that can occur. We propose a new methodology combining microcalorimetric measurements and molecular modelling to better describe the nature and strength of these interactions in these complex fluids by focusing on extractant-diluent mixtures (N,N-dialkylamides + n-alkanes). Enthalpies of dilution were obtained by microcalorimetric measurements at 298 K for each n-dodecane and n-heptane with DEHiBA and for n-dodecane with DEHBA. These results have been compared, thanks to a new method that we present here, to molecular dynamics simulations carried out on these same systems. We especially analyzed the influence of the alkyl branching of the extracting molecules and the role of the diluent. Globally, the excess enthalpy is such that these mixtures are energetically not very different from regular solutions but the detailed balance shows an important attraction between the extractants, which can lead to the formation of macromolecular entities favouring extraction. Calorimetry appears to be a method of choice for linking experiments and molecular modelling in these complex liquid mixtures, and experimental developments could benefit from using it more often, especially to validate force-fields.

Allosteric conformational ensembles have unlimited capacity for integrating information.

Integration of binding information by macromolecular entities is fundamental to cellular functionality. Recent work has shown that such integration cannot be explained by pairwise cooperativities, in which binding is modulated by binding at another site. Higher-order cooperativities (HOCs), in which binding is collectively modulated by multiple other binding events, appear to be necessary but an appropriate mechanism has been lacking. We show here that HOCs arise through allostery, in which effective cooperativity emerges indirectly from an ensemble of dynamically interchanging conformations. Conformational ensembles play important roles in many cellular processes but their integrative capabilities remain poorly understood. We show that sufficiently complex ensembles can implement any form of information integration achievable without energy expenditure, including all patterns of HOCs. Our results provide a rigorous biophysical foundation for analysing the integration of binding information through allostery. We discuss the implications for eukaryotic gene regulation, where complex conformational dynamics accompanies widespread information integration.

Modulation of Properties through Covalent Bond Induced Formation of Strong Ion Pairing between Polyelectrolytes in Injectable Conetwork Hydrogels.

In situ simultaneous formation of both covalent linkages and ion pair is challenging yet necessary to control the biological properties of a hydrogel. We report that the generation of covalent linkages (+N-C) facilitates the simultaneous formation of ion pairs between polyelectrolytes (PEs) in a hydrogel network. Co-injection of tertiary amine functional macromolecules and reactive poly(ethylene glycol) (PEG) containing negatively charged PE leads to the formation of hydrogel conetworks consisting of covalent junctions and ion pairs. Our design is based on the gradual appearance of +N-C junctions followed by formation of ion pairs. This strategy provides an easy access to hydrogel networks bearing a predetermined proportion of ion pair and covalent cross-linking junction. The proportion of ion pair could be varied by introducing a precalculated proportion of mono- and difunctional reactive PEG in the hydrogel system. The topology of the prepolymer and the hydrogel could be modulated (graft) during hydrogel formation. This approach is applicable to obtain covalent/ionic, covalent bond induced purely ionic, and purely covalent hydrogels of several macromolecular entities. The effect of ion pairing in the hydrogels is strongly reflected in the modulus, strain bearing, degradation, free volume, swelling, and drug release properties. The hydrogels exhibit microscopic recovery of modulus after application of high amplitude strain depending on the prepolymer concentration (chain entanglement) and nature of hydrogel network. The hydrogels are hemocompatible, and the covalent/ionic hydrogels show a slower release of methotrexate than that of the purely covalent hydrogel. This work provides an understanding for the in situ construction and manipulation of biological properties of hydrogels through the covalent bond induced formation of a strong ion pair.

Improved Rate for the Oxygen Reduction Reaction in a Sulfuric Acid Electrolyte using a Pt(111) Surface Modified with Melamine.

The feasible commercialization of alkaline, phosphoric acid and polymer electrolyte membrane fuel cells depends on the development of oxygen reduction reaction (ORR) electrocatalysts with improved activity, stability, and selectivity. The rational design of surfaces to ensure these improved ORR catalytic requirements relies on the so-called "descriptors" (e.g., the role of covalent and noncovalent interactions on platinum surface active sites for ORR). Here, we demonstrate that through the molecular adsorption of melamine onto the Pt(111) surface [Pt(111)-Mad], the activity can be improved by a factor of 20 compared to bare Pt(111) for the ORR in a strongly adsorbing sulfuric acid solution. The Mad moieties act as "surface-blocking bodies," selectively hindering the adsorption of (bi)sulfate anions (well-known poisoning spectator of the Pt(111) active sites) while the ORR is unhindered. This modified surface is further demonstrated to exhibit improved chemical stability relative to Pt(111) patterned with cyanide species (CNad), previously shown by our group to have a similar ORR activity increase compared to bare Pt(111) in a sulfuric acid electrolyte, with Pt(111)-Mad retaining a greater than ninefold higher ORR activity relative to bare Pt(111) after extensive potential cycling as compared to a greater than threefold higher activity retained on a CNad-covered Pt(111) surface. We suggest that the higher stability of the Pt(111)-Mad interface stems from melamine's ability to form intermolecular hydrogen bonds, which effectively turns the melamine molecules into larger macromolecular entities with multiple anchoring sites and thus more difficult to remove.

Approaches for the inhibition and elimination of microbial biofilms using macromolecular agents.

Biofilms are complex three-dimensional structures formed at interfaces by the vast majority of bacteria and fungi. These robust communities have an important detrimental impact on a wide range of industries and other facets of our daily lives, yet their removal is challenging owing to the high tolerance of biofilms towards conventional antimicrobial agents. This key issue has driven an urgent search for new innovative antibiofilm materials. Amongst these emerging approaches are highly promising materials that employ aqueous-soluble macromolecules, including peptides, proteins, synthetic polymers, and nanomaterials thereof, which exhibit a range of functionalities that can inhibit biofilm formation or detach and destroy organisms residing within established biofilms. In this Review, we outline the progress made in inhibiting and removing biofilms using macromolecular approaches, including a spotlight on cutting-edge materials that respond to environmental stimuli for "on-demand" antibiofilm activity, as well as synergistic multi-action antibiofilm materials. We also highlight materials that imitate and harness naturally derived species to achieve new and improved biomimetic and biohybrid antibiofilm materials. Finally, we share some speculative insights into possible future directions for this exciting and highly significant field of research.

Library of Derivatizable Multiblock Copolymers by Nucleophilic Substitution Polymerization and Targeting Specific Properties.

Multiblock copolymers (MBCs) are fascinating in the field of biology-polymer chemistry interfaces. Synthesizing libraries of MBCs with tailor-made functionality is challenging as it involves multiple steps. Herein, a simple synthesis, analogous to polyurethane/Michael addition reactions, has been introduced to obtain a library of derivatizable MBCs. Nucleophilic substitution polymerization (SNP) of poly(ε-caprolactone) and poly(ethylene glycol) blocks containing activated halide termini by primary mono/di/coamines or clickable amines provides functional MBCs. The structure of amines directs the properties of the MBCs. The self-assembly of small molecular weight primary diamine-based MBCs shows controlled release of hydrophobic model guest molecules and therapeutics. The primary diamine (no dangling chain) helps to form MBC micelles having a relatively tight core with a low diffusion property. Antimicrobial property in the MBCs has been introduced by separating the cationic centers from the lipophilic groups using a coamine as a nucleophilic agent and a small molecular weight dihalide as a chain extender. Clickable MBCs were synthesized by changing the structure of the nucleophile to obtain degradable amphiphilic conetworks and hydrogels. Varieties of macromolecular entities could be obtained by switching the nucleophilic agent and introducing a small molecular weight chain extender. This synthesis approach provides an opportunity to tune the chemical functionality, topological structure, and biological properties of macromolecular entities.

MIPs for commercial application in low-cost sensors and assays – An overview of the current status quo

Molecularly imprinted polymers (MIPs) have emerged over the past few decades as interesting synthetic alternatives due to their long-term chemical and physical stability and low-cost synthesis procedure. They have been integrated into many sensing platforms and assay formats for the detection of various targets, ranging from small molecules to macromolecular entities such as pathogens and whole cells. Despite the advantages MIPs have over natural receptors in terms of commercialization, the striking success stories of biosensor applications such as the glucose meter or the self-test for pregnancy have not been matched by MIP-based sensor or detection kits yet. In this review, we zoom in on the commercial potential of MIP technology and aim to summarize the latest developments in their commercialization and integration into sensors and assays with high commercial potential. We will also analyze which bottlenecks are inflicting with commercialization and how recent advances in commercial MIP synthesis could overcome these obstacles in order for MIPs to truly achieve their commercial potential in the near future.

PEGylated gold nanoparticles promoted rapid macromolecular chain-end transformation and formation of injectable hydrogels.

Azide-alkyne click cycloaddition and Michael addition reactions are useful for the synthesis and modification of biologically relevant macromolecules. Acceleration of these reactions at the macromolecular chain-ends and backbone has been achieved by gold [Au-(PEG-SH)n] nanoparticles (NPs) stabilized with multi-thiol-functional poly(ethylene glycol) containing tertiary amine groups in its backbone. The Au NPs successfully activate electron rich alkyne and acrylate functionalities of macromolecules at low substrate concentration leading to the enhancement of the reaction rate. The Au NPs successfully accelerate the gelation rate of reactive prepolymers leading to the rapid formation of injectable hydrogels. The Au nanocomposite hydrogels exhibited higher ultimate modulus and porosity than those of the pristine hydrogels. The grafting density (chains per nm2) of the stabilizer onto the Au NP surface plays a crucial role towards the activity of the NPs. The conversion of the chain-end functionality and gelation rate increase with decreasing grafting density onto the NP surface. A high grafting density lowers the activity of the Au NPs through blocking the active metal surface. The developed Au NPs may be a potential agent for the rapid preparation of biologically relevant macromolecular entities.

Multiscale Solutions to Quantitative Systems Biology Models.

Systems biology implements a variety of statistical, computational and mathematical techniques to understand how networks of biological systems work together to achieve a function (Westerhoff and Palsson, 2004; Wolkenhauer, 2014). Systems biology is a multi-scale field, as it has no fixed scale in the context of a biological response or cascade, where an ensemble of proteins, cofactors and small molecules concertedly act to achieve function. This is the case of fundamental pathophysiological networks, such as epidemiological responses with host and pathogens (Hillmer, 2015). Understanding the network of interactions that mediate these systems is of the utmost importance for deciphering the mechanisms associated with multifactorial diseases, as well as to address fundamental biological questions. This knowledge can be used for translational research and application in biomedicine (McGillivray et al., 2018). The multi-scale nature of systems biology calls for a multifaced description to bridge the system scale at the cellular level to the molecular scale of individual macromolecules. Among the important biological cascades responsible for severe diseases, we focus here on the complement system, which is an effector arm of the immune system that eliminates pathogens, helps in maintaining host homeostasis, and forms a bridge between innate and adaptive immunity (Bennett et al., 2017; Reis et al., 2019). Complement is composed of three pathways known as alternative, classical and lectin that work in concert to achieve its function (Schatz-Jakobsen et al., 2016a). The complex network of proteins and other macromolecular entities composing the complement system represents an ideal case to build a systems biology workflow predicting the system's response in immunity against invading pathogens, and how under complement deficiencies this same system mediates different pathologies. Here, we report on the development of systems biology predictive models, which describe the intricate biochemical networks and the crosstalk among other elements of the immune system. We also show how the integration of multiscale modeling techniques can help for improving the predictive model, while also providing mechanistic information at the molecular level. Complement dysfunction is associated with several diseases. Among others, the complement components have been associated with neurodegenerative disorders including Alzheimer and Parkinson diseases; as well as multiple sclerosis (Mastellos et al., 2019). Moreover, mutations of complement proteins have been linked to the etiology of renal diseases (De Vriese et al., 2015; Ricklin et al., 2016), while individuals with complement deficiencies develop severe infections, such as meningitis, bacteremia and pneumonia caused by microorganisms, such as Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus (Skattum et al., 2011). Clearly, while a proper activation of the complement system is associated with a wide spectrum of beneficial effects, dysfunctional states are associated with severe consequences. Considering that the function of the complement system is regulated by a network of multiple components, whose concerted activity underlies a variety of diseases, accurate models of the interaction network would greatly help therapeutic strategies (Ricklin et al., 2018).

Light-Induced Therapies for Prostate Cancer Treatment.

Prostate cancer (PC) is one of the most widespread tumors affecting the urinary system and the fifth-leading cause from cancer death in men worldwide. Despite PC mortality rates have been decreasing during the last years, most likely due to an intensification of early diagnosis, still more than 300,000 men die each year because of this disease. In this view, researchers in all countries are engaged in finding new ways to tackle PC, including the design and synthesis of novel molecular and macromolecular entities able to challenge different PC biological targets, while limiting the extent of unwanted side effects that significantly limit men's life quality. Among this field of research, photo-induced therapies, such as photodynamic and photothermal therapies (PDT and PTT), might represent an important advancement in PC treatment due to their extremely localized and controlled cytotoxic effect, as well as their low incidence of side effects and tumor resistance occurrence. Based on these considerations, this review aims to gather and discuss the last 5-years literature reports dealing with the synthesis and biological activity of molecular conjugates and nano-platforms for photo-induced therapies as co-adjuvant or combined therapeutic modalities for the treatment of localized PC.

Complexes of Zn(II)-Triazoles with CO2 and H2O: Structures, Energetics, and Applications.

Using a first-principle methodology, we investigate the stable structures of the nonreactive and reactive clusters formed between Zn2+-triazoles ([Zn2+-Tz]) clusters and CO2 and/or H2O. In sum, we characterized two modes of bonding of [Zn2+-Tz] with CO2/H2O: the interaction is established through (i) a covalent bond between Zn2+ of [Zn2+-Tz] and oxygen atoms of CO2 or H2O and (ii) hydrogen bonds through N-H or C-H of [Zn2+-Tz] and oxygen atoms of H2O or CO2, N-H···O. We also identified intramolecular proton transfer processes induced by complexation. Indeed, water drastically changes the shape of the energy profiles of the tautomeric phenomena through strong lowering of the potential barriers to tautomerism. The comparison to [Zn2+-Im] subunits formed with Zn2+ and imidazole shows that the efficiency of Tz-based compounds for CO2 capture and uptake is due to the incorporation of more accessible nitrogen donor sites in Tzs compared to imidazoles. Since [Zn2+-Tz] clusters are subunits of an organometallic nanoporous materials and Zn-proteins, our data are useful for deriving force fields for macromolecular simulations of these materials. Our work also suggests the consideration of traces of water to better model the CO2 sequestration and reactivity on macromolecular entities such as pores or active sites.

Micropatterned Viral Membrane Clusters for Antiviral Drug Evaluation.

The function of biological nanoparticles, such as membrane-enveloped viral particles, is often enhanced when the particles form higher-order supramolecular assemblies. While there is intense interest in developing biomimetic platforms that recapitulate these collective properties, existing platforms are limited to mimicking individual virus particles. Here, we present a micropatterning strategy to print linker molecules selectively onto bioinert surfaces, thereby enabling controlled tethering of biomimetic viral particle clusters across defined geometric patterns. By controlling the linker concentration, it is possible to tune the density of tethered particles within clusters while enhancing the signal intensity of encapsulated fluorescent markers. Time-resolved tracking of pore formation and membrane lysis revealed that an antiviral peptide can disturb clusters of the membrane-enclosed particles akin to the targeting of individual viral particles. This platform is broadly useful for evaluating the performance of membrane-active antiviral drug candidates, whereas the micropatterning strategy can be applied to a wide range of biological nanoparticles and other macromolecular entities.

Role of viral RNA in virion stability and disassembly

Viruses are metastable macromolecular entities that are assembled into compact particles. Entry into a target host cell initiates quaternary conformational changes in response to distinct host‐specific environmental changes including temperature, pH, osmolality, divalent cation concentrations, which promote disassembly and release of the virion's genome into the host cell. This host stimulus‐triggered disassembly is critical for initiating the infectious phase of the particle. How viruses use their quaternary coat protein structures as thermodynamic sensors for detecting entry into a conducive host cell environment is largely unknown. The process of viral disassembly is largely impervious to static structural methods as these only capture end‐state conformations. Amide Hydrogen Deuterium Exchange Mass Spectrometry (HDXMS) can be used to monitor whole viral particle dynamics in solution. The disassembling virion represents the virus at its most vulnerable state and is consequently a transient dynamic intermediate. A map of the quaternary structural changes in this state offers critical insights into cryptic epitopes as novel vaccine targets. Our research has pioneered structural mass spectrometry characterization of temperature and divalent cation‐dependent conformational changes on Dengue virus and Turnip Crinkle Virus (TCV) and mapped the specific disassembly processes in these two model virus systems. We have extended these studies to deconstruct the whole viral particle‐antibody (DENV2‐2D22) complex. Our results reveal the high intrinsic dynamics of the RNA packing capsid C‐protein which underpins viral transition from compact to expanded states in the process of disassembly. We have also uncovered new disassembly intermediates triggered by varying monovalent and divalent cation concentrations. Viral disassembly processes in TCV and Dengue reveal conformations of disassembly intermediates which represent powerful new targets for therapeutic antibody design as well as offer fundamental insights into strategically timed viral disassembly processes which can be extended to all viruses.Support or Funding InformationSingapore Ministry of Education Tier 3 grantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Virion Capsid Dynamics and Quaternary Conformational Changes Upon Host Entry

Viruses are metastable macromolecular entities that are assembled into compact particles. Entry into a target host cell initiates quaternary conformational changes in response to distinct host-specific environmental changes including temperature, pH, osmolality, divalent cation concentrations, which promote disassembly and release of the virion's genome into the host cell. This host stimulus-triggered disassembly is critical for initiating the infectious phase of the particle. How viruses use their quaternary coat protein structures as thermodynamic sensors for detecting entry into a conducive host cell environment is largely unknown. The process of viral disassembly is largely impervious to static structural methods as these only capture end-state conformations. Amide Hydrogen Deuterium Exchange Mass Spectrometry (HDXMS) can be used to monitor whole viral particle dynamics in solution. The disassembling virion represents the virus at its most vulnerable state and is consequently a transient dynamic intermediate. A map of the quaternary structural changes in this state offers critical insights into cryptic epitopes as novel vaccine targets. Our research has pioneered structural mass spectrometry characterization of temperature and divalent cation-dependent conformational changes on Dengue virus and Turnip Crinkle Virus (TCV) and mapped the specific disassembly processes in these two model virus systems. We have extended these studies to deconstruct the whole viral particle-antibody (DENV2-2D22) complex. Our results reveal the high intrinsic dynamics of the RNA packing capsid C-protein which underpins viral transition from compact to expanded states in the process of disassembly. We have also uncovered new disassembly intermediates triggered by varying monovalent and divalent cation concentrations. Viral disassembly processes in TCV and Dengue reveal conformations of disassembly intermediates which represent powerful new targets for therapeutic antibody design as well as offer fundamental insights into strategically timed viral disassembly processes which can be extended to all viruses.

Inhibitors of kallikrein-related peptidases: An overview.

Kallikrein-related peptidases (KLKs) are a family of 15 secreted serine proteases that are involved in various physiological processes. Their activities are subtly regulated by various endogenous inhibitors, ranging from metallic ions to macromolecular entities such as proteins. Furthermore, dysregulation of KLK activity has been linked to several pathologies, including cancer and skin and inflammatory diseases, explaining the numerous efforts to develop KLK-specific pharmacological inhibitors as potential therapeutic agents. In this review, we focus on the huge repertoire of KLKs inhibitors reported to date with a special emphasis on the diversity of their molecular mechanisms of inhibition.

Effect of the chain length of the molecule of saturated hydrocarbons on the chemical structure and morphology of polymer films formed in low temperature plasma

Previously, we have investigated the formation of polymer films from heptane on the surface of a metal substrate in low-temperature plasma (LTP) by varying the mode and time of plasma treatment [1–3]. It was found that the formation of the films occurs in three stages, each being characterized by certain topography, chemical structure, and mechanical properties of the films. In the first stage, continuous films are formed that mimic the substrate topography, smoothing it. The films are homogeneous in their chemical structure, have a low hardness, high permeability, and hydrophilicity. In the second stage, the films grow via the formation of isolated macromolecular entities, “islets.” At the end of the second step, the entire surface of the films is covered by the islets, and the films have a maximum hardness, low permeability, and hydrophobicity. In the third stage, the polymer chains undergo degradation accompanied by the intense etching of the film, which manifest itself in a reduction of its thickness, smoothing of the topography, enhancement of permeability, and surface hydrophilicity. In this study, we examined the effect of the chain length of saturated hydrocarbon molecules on the chemical structure and morphology of the polymer films formed in low-temperature plasma.

Improving the Stability and Activity of Oral Therapeutic Enzymes—Recent Advances and Perspectives

Exogenous, orally-administered enzymes are currently in clinical use or under development for the treatment of pathologies, such as celiac disease and phenylketonuria. However, the administration of therapeutic enzymes via the oral route remains challenging due to potential inactivation of these fragile macromolecular entities in the harsh environment of the gastrointestinal tract. Enzymes are particularly sensitive because both proteolysis and unfolding can lead to their inactivation. Current efforts to overcome these shortcomings involve the application of gastro-resistant delivery systems and the modification of enzyme structures by polymer conjugation or protein engineering. This perspective manuscript reviews and critically discusses recent progress in the oral delivery of therapeutic enzymes, whose substrate is localized in the gastrointestinal tract.