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1.
Yurkovetskiy A Choi S Hiller A Yin M McCusker C Syed S Fischman AJ Papisov MI 《Biomacromolecules》2005,6(5):2648-2658
Modification of proteins with hydrophilic polymers is an effective strategy for regulation of protein pharmacokinetics. However, conjugates of slowly or non-biodegradable materials, such as poly(ethylene glycol), are known to cause long-lasting cell vacuolization, in particular in renal epithelium. Conjugates of more degradable polymers, e.g., polysaccharides, have a significant risk of immunotoxicity. Polymers that combine complete degradability, long circulation in vivo, and low immuno and chemical toxicity would be most beneficial as protein conjugate components. This study explores new fully biodegradable hydrophilic polymers, hydrophilic polyals. They are nontoxic, stable at physiological conditions, and undergo proton-catalyzed hydrolysis at lysosomal pH. The model enzyme-polyal conjugates were prepared with 61-98% yield using conventional and novel conjugation techniques and retained 90-95% of specific activity. The model conjugates showed a significant prolongation of protein circulation in rodents, with a 5-fold reduction in the renal accumulation. The data suggests that hydrophilic polyals may be useful in designing protein conjugates with improved properties. 相似文献
2.
The (2-azidomethyl)phenylacetyl group (AMPA) is described as a new protecting group for carbohydrates. AMPA was introduced to carbohydrate hydroxyl groups in the presence of DCC, while its removal was conveniently achieved via Lindlar catalyst-catalyzed hydrogenation that had no influence on other protecting groups including benzyl, acyl, acetal and ketal. 相似文献
3.
In this report, we present an acid-sensitive drug delivery vehicle, termed polyketal nanoparticles, which are designed to target therapeutics to the acidic environments of tumors, inflammatory tissues, and phagosomes. The polyketal nanoparticles are formulated from poly(1,4-phenyleneacetone dimethylene ketal) (PPADK), a new hydrophobic polymer which contains ketal linkages in its backbone. The polyketal nanoparticles undergo acid-catalyzed hydrolysis into low molecular weight hydrophilic compounds and should therefore release encapsulated therapeutics at an accelerated rate in acidic environments. Importantly, the polyketal nanoparticles do not generate acidic degradation products after hydrolysis, as with polyester-based biomaterials. Dexamethasone-loaded nanoparticles, 200-600 nm in diameter, were fabricated with PPADK via an emulsion procedure using chloroform and water. The hydrolysis half-life of PPADK was measured to be 102 h at pH 7.4 and 35 h at pH 5.0. PPADK was synthesized by a new polymerization strategy based on the acetal exchange reaction. This new delivery system should find numerous applications in the field of drug delivery because of its ease of synthesis and excellent degradation properties. 相似文献
4.
Monosaccharides and amino acids are fundamental building blocks in the assembly of nature's polymers. They have different structural aspects and, to a significant extent, different functional groups. Oligomerization gives rise to oligosaccharides and peptides, respectively. While carbohydrates and peptides can be found conjoined in nature, e.g., in glycopeptides, the aim of this review is the radical redesign of peptide structures using carbohydrates, particularly monosaccharides and cyclic oligosaccharides, to produce novel peptides, peptidomimetics, and abiotic proteins. These hybrid molecules, chimeras, have properties arising largely from the combination of structural characteristics of carbohydrates with the functional group diversity of peptides. This field includes de novo designed synthetic glycopeptides, sugar (carbohydrate) amino acids, carbohydrate scaffolds for nonpeptidal peptidomimetics of cyclic peptides, cyclodextrin functionalized peptides, and carboproteins, i.e., carbohydrate-based proteinmimetics. These successful applications demonstrate the general utility of carbohydrates in peptide and protein architecture. 相似文献
5.
Currently, biomedical engineering is rapidly expanding, especially in the areas of drug delivery, gene transfer, tissue engineering, and regenerative medicine. A prerequisite for further development is the design and synthesis of novel multifunctional biomaterials that are biocompatible and biologically active, are biodegradable with a controlled degradation rate, and have tunable mechanical properties. In the past decades, different types of α-amino acid-containing degradable polymers have been actively developed with the aim to obtain biomimicking functional biomaterials. The use of α-amino acids as building units for degradable polymers may offer several advantages: (i) imparting chemical functionality, such as hydroxyl, amine, carboxyl, and thiol groups, which not only results in improved hydrophilicity and possible interactions with proteins and genes, but also facilitates further modification with bioactive molecules (e.g., drugs or biological cues); (ii) possibly improving materials biological properties, including cell-materials interactions (e.g., cell adhesion, migration) and degradability; (iii) enhancing thermal and mechanical properties; and (iv) providing metabolizable building units/blocks. In this paper, recent developments in the field of α-amino acid-containing degradable polymers are reviewed. First, synthetic approaches to prepare α-amino acid-containing degradable polymers will be discussed. Subsequently, the biomedical applications of these polymers in areas such as drug delivery, gene delivery and tissue engineering will be reviewed. Finally, the future perspectives of α-amino acid-containing degradable polymers will be evaluated. 相似文献
6.
《Biotechnology advances》2017,35(4):450-457
Increased health risk associated with the sedentary life style is forcing the food manufacturers to look for food products with specific or general health benefits e.g. beverages enriched with nutraceuticals like catechin, curcumin rutin. Compounds like polyphenols, flavonoids, vitamins are the good choice of bioactive compounds that can be used to fortify the food products to enhance their functionality. However due to low stability and bioavailability of these bioactives (both hydrophobic and hydrophilic) within the heterogeneous food microstructure and in the Gastro Intestinal Tract (GIT), it becomes extremely difficult to pass on the real health benefits to the consumers.Recent developments in the application of nano-delivery systems for food product development is proving to be a game changer which has raised the expectations of the researchers, food manufacturers and consumers regarding possibility of enhancing the functionality of bioactives within the fortified food products. In this direction, nano/micro delivery systems using lipids, surfactants and other materials (carbohydrates, polymers, complexes, protein) have been fabricated to stabilize and enhance the biological activity of the bioactive compounds.In the present review, current status of the various delivery systems that are used for the delivery of hydrophilic bioactives and future prospects for using other delivery systems that have been not completely explored for the delivery of hydrophilic bioactives e.g. niosomes; bilosomes, cubosomes are discussed. 相似文献
7.
Modification of proteins with polymers is a viable method to tune protein properties, e.g., to render them more water-soluble by using hydrophilic polymers. We have utilized precision-length, polyethylene glycol-based oligomers carrying a thioester moiety in transthioesterification and native chemical ligation reactions with internal and N-terminal cysteine residues in proteins and peptides. These reactions lead to uniquely modified proteins with an increased solubility in chaotrope- and detergent-free aqueous systems. Polymer modification of internal cysteines is fully reversible and allows generation of stable protein-polymer conjugates for enzymatic manipulations as demonstrated by proteolytic cleavage of a protein construct that was only soluble in buffers incompatible with protease activity before polymer modification. The permanent polymer modification of a Rab protein at its N-terminal cysteine produced a fully active Rab variant that was efficiently prenylated. Thus, PEGylation of prenylated proteins might be a viable route to increase water solubility of such proteins in order to carry out experiments in detergent- and lipid-free systems. 相似文献
8.
Extracellular polymeric substances (EPS) of microbial aggregates in biological wastewater treatment systems: A review 总被引:11,自引:0,他引:11
A review concerning the definition, extraction, characterization, production and functions of extracellular polymeric substances (EPS) of microbial aggregates in biological wastewater treatment reactors is given in this paper. EPS are a complex high-molecular-weight mixture of polymers excreted by microorganisms, produced from cell lysis and adsorbed organic matter from wastewater. They are a major component in microbial aggregates for keeping them together in a three-dimensional matrix. Their characteristics (e.g., adsorption abilities, biodegradability and hydrophilicity/hydrophobicity) and the contents of the main components (e.g., carbohydrates, proteins, humic substances and nucleic acids) in EPS are found to crucially affect the properties of microbial aggregates, such as mass transfer, surface characteristics, adsorption ability, stability, the formation of microbial aggregates etc. However, as EPS are very complex, the knowledge regarding EPS is far from complete and much work is still required to fully understand their precise roles in the biological treatment process. 相似文献
9.
This paper demonstrates that miscible blends from water-insoluble polymers, such as poly(2,4,4-trimethylhexamethylene terephthalamide) (1), methylamine imidized poly(methyl methacrylate) (2), and aromatic poly(ether sulfone) (3) and water-soluble polymers, such as poly(2-ethyl-2-oxazoline) (4) and poly(N-vinyl pyrrolidone) (5), respectively, represent a new class of supramolecular hydrogels. When the degree of polymerization (DP) of the water-soluble polymer is larger than that of water-insoluble polymer, the resulting hydrogels adsorb extremely high amounts of water (i.e., 229 wt % in the case of the hydrogel 1/4) and remain mechanically tough. The high water uptake capability of these blends is explained by a supramolecular network structure generated by H-bonding and/or other noncovalent interactions between the water-insoluble hydrophobic polymer and water-soluble hydrophilic segments as reversible cross-linking points interconnected by hydrophilic water soluble segments. The glass transition temperatures of these hydrogels are tailored via the ratio between the weight percent of the two polymers and by the glass transition temperature of the parent polymers. These supramolecular hydrogels can be processed from melt or solution and maintain excellent mechanical properties both in dry and in the water swollen state. This class of hydrogels is of interest for areas such as membranes, contact lenses, tissue engineering, and other biomedical applications. 相似文献
10.
The CD spectra are reported for a series of 1,3-dioxane-type 4,6-O-(2'-naphthyl)methylene acetals of carbohydrates with and without interacting aromatic protective groups on the C-1, C-2, and C-3 hydroxy groups. In the absence of interacting chromophores, the signs of the (1)B transitions are not sensitive to the configuration of C-4, while the signs of the weak (1)L(a) bands are opposite in the galacto and gluco derivatives. The equatorial parallel conformation is found to be the preferred conformation of the 2-naphthyl group in the solid state by X-ray diffraction. The intense (1)B(a) and (1)B(b) transitions of the naphthalene chromophore allowed a safe configurational assignment by exciton coupled interaction with the aromatic protective groups in para-methoxyphenyl-beta-D-glycosides. The origin of the observed CEs were deduced and the additivity of the interactions was studied. The direction of the hydrogenolytic cleavage of 4,6-O-(2'-naphthyl)methylene acetal of carbohydrates could also be detected by the (1)B(b) transition of the 2-naphthyl chromophore. 相似文献
11.
Polysaccharides are being processed into biomaterials for numerous biological applications due to their native source in numerous tissues and biological functions. For instance, hyaluronic acid (HA) is found abundantly in the body, interacts with cells through surface receptors, and can regulate cellular behavior (e.g., proliferation, migration). HA was previously modified with reactive groups to form hydrogels that are degraded by hyaluronidases, either added exogenously or produced by cells. However, these hydrogels may be inhibitory and their applications are limited if the appropriate enzymes are not present. Here, for the first time, we synthesized HA macromers and hydrogels that are both hydrolytically (via ester group hydrolysis) and enzymatically degradable. The hydrogel degradation and growth factor release was tailored through the hydrogel cross-linking density (i.e., macromer concentration) and copolymerization with purely enzymatically degradable macromers. When mesenchymal stem cells (MSCs) were encapsulated in the hydrogels, cellular organization and tissue distribution was influenced by the copolymer concentration. Importantly, the distribution of released extracellular matrix molecules (e.g., chondroitin sulfate) was improved with increasing amounts of the hydrolytically degradable component. Overall, this new macromer allows for enhanced control over the structural evolution of the HA hydrogels toward applications as biomaterials. 相似文献
12.
Two types of acid-degradable nonviral gene carriers, OEI-MK and OEI-BAA, were synthesized by polymerizing oligoethylenimine of 800 Da (OEI800) with the pH-sensitive acetone ketal cross-linker 2,2-bis(N-maleimidoethyloxy) propane (MK) or the 4-methoxybenzaldehyde bisacrylate acetal cross-linker 1,1-bis-(2-acryloyloxy ethoxy)-[4-methoxy-phenyl]methane) (BAA). Corresponding acid-insensitive counterparts (OEI-BM and LT-OEI-HD) were synthesized as well, representing control polymers. Kinetics of hydrolysis were measured and confirmed the pH-dependent degradation profile of the acetal functions, with short half-lives of 3 min at pH 5.0, and 5 h (OEI-MK) or 3.5 h (OEI-BAA) at physiological pH 7.4 and 37 degrees C. DNA polyplexes of a luciferase expression plasmid were tested for gene transfer efficiency and biocompatibility in two cell lines (B16F10 and Neuro2A). Polyplexes with acid-labile polymers showed an improved toxicity profile compared to those made with acid-stable polymer analogues. At low cation/plasmid (c/p) w/w ratios the transfection efficiency of pH-sensitive polymers was slightly reduced, but it became similar or superior to the efficiency of acid-stable polymers at higher c/p ratios. An improved in vivo biocompatibility of the acid-degradable polymers over the stable control polymers was confirmed by liver histology after systemic administration of polymers in Balb/c mice. 相似文献
13.
Physicochemical properties of polymers: An important system to overcome the cell barriers in gene transfection
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Delivery of the macromolecules including DNA, miRNA, and antisense oligonucleotides is typically mediated by carriers due to the large size and negative charge. Different physical (e.g., gene gun or electroporation), and chemical (e.g., cationic polymer or lipid) vectors have been already used to improve the efficiency of gene transfer. Polymer‐based DNA delivery systems have attracted special interest, in particular via intravenous injection with many intra‐ and extracellular barriers. The recent progress has shown that stimuli‐responsive polymers entitled as multifunctional nucleic acid vehicles can act to target specific cells. These nonviral carriers are classified by the type of stimulus including reduction potential, pH, and temperature. Generally, the physicochemical characterization of DNA‐polymer complexes is critical to enhance the transfection potency via protection of DNA from nuclease digestion, endosomal escape, and nuclear localization. The successful clinical applications will depend on an exact insight of barriers in gene delivery and development of carriers overcoming these barriers. Consequently, improvement of novel cationic polymers with low toxicity and effective for biomedical use has attracted a great attention in gene therapy. This article summarizes the main physicochemical and biological properties of polyplexes describing their gene transfection behavior, in vitro and in vivo. In this line, the relative efficiencies of various cationic polymers are compared. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 363–375, 2015. 相似文献
14.
A class of organic polymers, known as conducting polymers (CPs), has become increasingly popular due to its unique electrical and optical properties. Material characteristics of CPs are similar to those of some metals and inorganic semiconductors, while retaining polymer properties such as flexibility, and ease of processing and synthesis, generally associated with conventional polymers. Owing to these characteristics, research efforts in CPs have gained significant traction to produce several types of CPs since its discovery four decades ago. CPs are often categorised into different types based on the type of electric charges (e.g., delocalized pi electrons, ions, or conductive nanomaterials) responsible for conduction. Several CPs are known to interact with biological samples while maintaining good biocompatibility and hence, they qualify as interesting candidates for use in a numerous biological and medical applications. In this paper, we focus on CP-based sensor elements and the state-of-art of CP-based sensing devices that have potential applications as tools in clinical diagnosis and surgical interventions. Representative applications of CP-based sensors (electrochemical biosensor, tactile sensing 'skins', and thermal sensors) are briefly discussed. Finally, some of the key issues related to CP-based sensors are highlighted. 相似文献
15.
A hyperbranched conjugated polyelectrolyte (HCPE) with a core-shell structure is designed and synthesized via alkyne polycyclotrimerization and click chemistry. The HCPE has an emission maximum at 565 nm with a quantum yield of 12% and a large Stokes shift of 143 nm in water. By virtue of its poly(ethylene glycol) shell, this polymer naturally forms spherical nanoparticles that minimize nonspecific interaction with biomolecules in aqueous solution, consequently allowing for efficient bioconjugation with anti-HER2 affibody via carbodiimide-activated coupling reaction. The resulting affibody-attached HCPE can be utilized as a reliable fluorescent probe for targeted cellular imaging of HER2-overexpressed cancer cells such as SKBR-3. Considering its low cytotoxicity and good photostability, the HCPE nanoprobe holds great promise in practical imaging tasks. This study also provides a molecular engineering strategy to overcome the intrinsic limitations of traditional fluorescent polymers (e.g., chromophore-tethered polymers and linear conjugated polyelectrolytes) for bioconjugation and applications. 相似文献
16.
Liquid crystals based on fluorinated carbohydrates 总被引:3,自引:0,他引:3
Fluorine introduced in the hydrophilic or the hydrophobic region of amphiphiles influences the thermomesomorphy of amphiphilic and monophilic fluorosugars in a very specific manner. This paper is the first review about chiral mesogens based on fluorinated carbohydrates. It covers the literature published so far. Analytical objectives are given to: (i) Effects of fluorine atoms on the H-bonding network of the hydrophilic region of sugar amphiphiles; (ii) Effects of perfluoroalkyl chains compared to alkyl chains; (iii) Polymorphism, e.g., also formation of smectic S(C)* phases. 相似文献
17.
Superparamagnetic iron oxide nanoparticles (SPIONs) are excellent MR contrast agents when coated with biocompatible polymers such as hydrophilic synthetic polymers, proteins, polysaccharides, and lipids, which improve their stability and biocompatibility and reduce their aggregation. Various biocompatible materials, coated or conjugated with targeting moieties such as galactose, mannose, folic acid, antibodies and RGD, have been applied to SPION surfaces to provide tissue specificity to hepatocytes, macrophages, and tumor regions in order to reduce non-specific uptake and improve biocompatibility. This review discusses the recent progress in the development of biocompatible and hydrophilic polymers for improving stability of SPIONs and describes the carbohydrates based biocompatible materials that are providing SPIONs with cell/tissue specificity as ligands. 相似文献
18.
Infrared attenuated total reflection (ATR) spectroscopy may be used to investigate biological material (e.g., membranes, proteins, erythrocytes etc.) under biological conditions provided that adhesion of the sample can be achieved in aqueous environment. Uncharged lipid multilayer model membranes can be attached by hydrophobic interaction when hydrophobic internal reflection plates (e.g., ZnSe, CdTe) are used. However, if an electric field is applied across the membrane, germanium reflection elements would be preferred because of their low electric resistance (approximately 50 omega cm). This material can also be used if cells or proteins are linked chemically to the ATR plate because of the hydrophilic surface which is similar to that of glass and, thus, enables chemical modification by silanization. It has turned out that good adhesion of uncharged and negatively charged model membranes to germanium plates is achieved when they are coated with a monomolecular layer of aminopropylsilane. There is some evidence that erythrocytes remain more stable when adsorbed to a polymerized aminosilane coating (organic silanization) rather than to the corresponding monolayer (aqueous silanization). Negatively charged germanium surfaces have been obtained by succinylation of the aminosilane coating. Furthermore it has been demonstrated that proteins can be bound to the aminosilane coating by means of carbodiimide. Immobilized acetylcholinesterase was still enzymatically active. 相似文献
19.
Polymers based on carbohydrates have re-emerged as exciting topics of polymer research, due to a worldwide focus on sustainable materials. However, multi-step synthesis of these polymers have made their use as commodity plastics uneconomical, and currently their applications are restricted to biomedical fields. Functionalization of polymers has emerged as another important area of polymer science and technology. Chemically linking sugar moeities onto synthetic polymers is a unique method of functionalization of synthetic polymers, whereby not only is the polymer functionalized, but it can also get other desirable properties such as biodegradability—a property much debated and researched in modern times. This paper reviews several methods of anchoring carbohydrates onto polymers and the advantages and the disadvantages associated with each method, their current and potential applications, and their characterization methods. 相似文献
20.
As one of the most abundant polymers in biosphere, lignin has attracted extensive attention as a kind of promising feedstock for biofuel and bio-based products. However, the utilization of lignin presents various challenges in that its complex composition and structure and high resistance to degradation. Lignin conversion through biological platform harnesses the catalytic power of microorganisms to decompose complex lignin molecules and obtain value-added products through biosynthesis. Given the heterogeneity of lignin, various microbial metabolic pathways are involved in lignin bioconversion processes, which has been characterized in extensive research work. With different types of lignin substrates (e.g., model compounds, technical lignin, and lignocellulosic biomass), several bacterial and fungal species have been proved to own lignin-degrading abilities and accumulate microbial products (e.g., lipid and polyhydroxyalkanoates), while the lignin conversion efficiencies are still relatively low. Genetic and metabolic strategies have been developed to enhance lignin biodegradation by reprogramming microbial metabolism, and diverse products, such as vanillin and dicarboxylic acids were also produced from lignin. This article aims at presenting a comprehensive review on lignin bioconversion including lignin degradation mechanisms, metabolic pathways, and applications for the production of value-added bioproducts. Advanced techniques on genetic and metabolic engineering are also covered in the recent development of biological platforms for lignin utilization. To conclude this article, the existing challenges for efficient lignin bioprocessing are analyzed and possible directions for future work are proposed. 相似文献