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1.
Nat Commun ; 11(1): 4655, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938918

RESUMO

Purely organic room-temperature phosphorescence has attracted attention for bioimaging but can be quenched in aqueous systems. Here we report a water-soluble ultralong organic room-temperature phosphorescent supramolecular polymer by combining cucurbit[n]uril (CB[7], CB[8]) and hyaluronic acid (HA) as a tumor-targeting ligand conjugated to a 4-(4-bromophenyl)pyridin-1-ium bromide (BrBP) phosphor. The result shows that CB[7] mediated pseudorotaxane polymer CB[7]/HA-BrBP changes from small spherical aggregates to a linear array, whereas complexation with CB[8] results in biaxial pseudorotaxane polymer CB[8]/HA-BrBP which transforms to relatively large aggregates. Owing to the more stable 1:2 inclusion complex between CB[8] and BrBP and the multiple hydrogen bonds, this supramolecular polymer has ultralong purely organic RTP lifetime in water up to 4.33 ms with a quantum yield of 7.58%. Benefiting from the targeting property of HA, this supramolecular polymer is successfully applied for cancer cell targeted phosphorescence imaging of mitochondria.


Assuntos
Mitocôndrias/efeitos dos fármacos , Polímeros/química , Células A549 , Células HEK293 , Humanos , Ácido Hialurônico/química , Ligação de Hidrogênio , Medições Luminescentes , Microscopia Confocal , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Polímeros/metabolismo , Taxoides/química , Temperatura
2.
Nat Commun ; 11(1): 3048, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546688

RESUMO

Nanomaterials in the blood must mitigate the immune response to have a prolonged vascular residency in vivo. The composition of the protein corona that forms at the nano-biointerface may be directing this, however, the possible correlation of corona composition with blood residency is currently unknown. Here' we report a panel of new soft single molecule polymer nanomaterials (SMPNs) with varying circulation times in mice (t1/2ß ~ 22 to 65 h) and use proteomics to probe protein corona at the nano-biointerface to elucidate the mechanism of blood residency of nanomaterials. The composition of the protein opsonins on SMPNs is qualitatively and quantitatively dynamic with time in circulation. SMPNs that circulate longer are able to clear some of the initial surface-bound common opsonins, including immunoglobulins, complement, and coagulation proteins. This continuous remodelling of protein opsonins may be an important decisive step in directing elimination or residence of soft nanomaterials in vivo.


Assuntos
Materiais Biocompatíveis/farmacocinética , Nanoestruturas/administração & dosagem , Proteínas Opsonizantes/sangue , Polímeros/metabolismo , Administração Intravenosa , Animais , Circulação Sanguínea , Feminino , Meia-Vida , Humanos , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Proteínas Opsonizantes/química , Proteínas Opsonizantes/metabolismo , Polímeros/química , Coroa de Proteína/química , Coroa de Proteína/metabolismo , Espectrometria de Massas em Tandem , Distribuição Tecidual
3.
PLoS One ; 15(3): e0218302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191710

RESUMO

This study demonstrates that novel polymer production can be achieved by introducing pTAM, a broad-host-range plasmid expressing codon-optimized genes encoding Clostridium propionicum propionate CoA transferase (PctCp, Pct532) and a modified Pseudomonas sp. MBEL 6-19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1Ps6-19, PhaC1400), into phaC mutant strains of the native polymer producers Sinorhizobium meliloti and Pseudomonas putida. Both phenotypic analysis and gas chromatography analysis indicated the synthesis and accumulation of biopolymers in S. meliloti and P. putida strains. Expression in S. meliloti resulted in the production of PLA homopolymer up to 3.2% dried cell weight (DCW). The quaterpolymer P (3HB-co-LA-co-3HHx-co-3HO) was produced by expression in P. putida. The P. putida phaC mutant strain produced this type of polymer the most efficiently with polymer content of 42% DCW when cultured in defined media with the addition of sodium octanoate. This is the first report, to our knowledge, of the production of a range of different biopolymers using the same plasmid-based system in different backgrounds. In addition, it is the first time that the novel polymer (P(3HB-co-LA-co-3HHx-co-3HO)), has been reported being produced in bacteria.


Assuntos
Engenharia Genética , Ácido Láctico/metabolismo , Polímeros/metabolismo , Pseudomonas putida/metabolismo , Sinorhizobium meliloti/metabolismo , Caprilatos/farmacologia , Códon/genética , Fluorescência , Genes Bacterianos , Glucuronidase/metabolismo , Isopropiltiogalactosídeo/farmacologia , Fenótipo , Plasmídeos/metabolismo , Poliésteres/metabolismo , Poli-Hidroxialcanoatos/metabolismo , Pseudomonas putida/efeitos dos fármacos , Pseudomonas putida/genética , Sinorhizobium meliloti/efeitos dos fármacos , Sinorhizobium meliloti/genética
4.
Sci Adv ; 6(9): eaaz5757, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32158951

RESUMO

Some bacteria are recognized to produce useful substances and electric currents, offering a promising solution to environmental and energy problems. However, applications of high-performance microbial devices require a method to accumulate living bacteria into a higher-density condition in larger substrates. Here, we propose a method for the high-density assembly of bacteria (106 to 107 cells/cm2) with a high survival rate of 80 to 90% using laser-induced convection onto a self-organized honeycomb-like photothermal film. Furthermore, the electricity-producing bacteria can be optically assembled, and the electrical current can be increased by one to two orders of magnitude simply by increasing the number of laser irradiations. This concept can facilitate the development of high-density microbial energy conversion devices and provide new platforms for unconventional environmental technology.


Assuntos
Bactérias/metabolismo , Luz , Fontes de Energia Bioelétrica , Polímeros/metabolismo
5.
Science ; 367(6484): 1372-1376, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32193327

RESUMO

The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type-specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems.


Assuntos
Compostos de Anilina/química , Ascorbato Peroxidases/genética , Engenharia Genética , Neurônios/fisiologia , Nitrocompostos/química , Fenilenodiaminas/química , Polímeros/química , Potenciais de Ação , Animais , Ascorbato Peroxidases/metabolismo , Caenorhabditis elegans , Membrana Celular/metabolismo , Sobrevivência Celular , Células Cultivadas , Condutividade Elétrica , Células HEK293 , Hipocampo , Humanos , Potenciais da Membrana , Camundongos , Neurônios Motores/fisiologia , Células Musculares/fisiologia , Neurônios/enzimologia , Técnicas de Patch-Clamp , Polímeros/metabolismo , Ratos , Transdução Genética
6.
Nat Commun ; 11(1): 1408, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179732

RESUMO

In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its organization in vivo. Here, we perform molecular dynamics simulations for Caulobacter crescentus MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that successfully predicts MreB filament properties in vivo. Our analyses indicate that MreB double protofilaments can exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting correlates with the length and orientation of MreB filaments observed in vitro and in vivo. Our molecular dynamics simulations also suggest that membrane binding of MreB double protofilaments induces a stable membrane curvature of similar magnitude to that observed in vivo. Thus, our multiscale modeling correlates cytoskeletal filament size with conformational changes inferred from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular organization and function.


Assuntos
Proteínas de Bactérias/química , Caulobacter crescentus/metabolismo , Citoesqueleto/química , Polímeros/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fenômenos Biomecânicos , Caulobacter crescentus/química , Caulobacter crescentus/genética , Citoesqueleto/genética , Citoesqueleto/metabolismo , Simulação de Dinâmica Molecular , Polímeros/metabolismo , Rotação
7.
Food Chem ; 316: 126309, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32059165

RESUMO

Melanoidins are an important component of the human diet (average consumption 10 g/day), which escape gastrointestinal digestion and are fermented by the gut microbiota. In this study melanoidins from different food sources (coffee, bread, beer, balsamic vinegar, sweet wine, biscuit, chocolate, and breakfast cereals) were submitted to an in vitro digestion and fermentation process, and their bioactivity was assessed. Some melanoidins were extensively used by gut microbes, increasing production of short chain fatty acids (mainly acetate and lactate) and favoring growth of the beneficial genera Bifidobacterium (bread crust, pilsner and black beers, chocolate and sweet wine melanoidins) and Faecalibacterium (biscuit melanoidins). Quantification of individual phenolic compounds after in vitro fermentation allowed their identification as microbial metabolites or phenolics released from the melanoidins backbone (specially pyrogallol, 2-(3,4-dihydroxyphenyl)acetic and 3-(3,4-dihydroxyphenyl)propionic acids). Our results also showed that antioxidant capacity of melanoidins is affected by gut microbiota fermentation.


Assuntos
Microbioma Gastrointestinal , Polímeros/metabolismo , Antioxidantes/análise , Antioxidantes/metabolismo , Bifidobacterium/metabolismo , Dieta , Fermentação
8.
Microbes Environ ; 35(1)2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101840

RESUMO

The genome of Streptomyces scabies, the predominant causal agent of potato common scab, encodes a potential cutinase, the protein Sub1, which was previously shown to be specifically induced in the presence of suberin. The sub1 gene was expressed in Escherichia coli and the recombinant protein Sub1 was purified and characterized. The enzyme was shown to be versatile because it hydrolyzes a number of natural and synthetic substrates. Sub1 hydrolyzed p-nitrophenyl esters, with the hydrolysis of those harboring short carbon chains being the most effective. The Vmax and Km values of Sub1 for p-nitrophenyl butyrate were 2.36 mol g-1 min-1 and 5.7 10-4 M, respectively. Sub1 hydrolyzed the recalcitrant polymers cutin and suberin because the release of fatty acids from these substrates was observed following the incubation of the enzyme with these polymers. Furthermore, the hydrolyzing activity of the esterase Sub1 on the synthetic polymer polyethylene terephthalate (PET) was demonstrated by the release of terephthalic acid (TA). Sub1 activity on PET was markedly enhanced by the addition of Triton and was shown to be stable at 37°C for at least 20 d.


Assuntos
Proteínas de Bactérias/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Doenças das Plantas/microbiologia , Polímeros/metabolismo , Streptomyces/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/isolamento & purificação , Ácidos Graxos/metabolismo , Hidrólise , Ácidos Ftálicos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Solanum tuberosum/microbiologia , Streptomyces/genética
9.
Chemistry ; 26(32): 7323-7329, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32074397

RESUMO

Molecular hydrogen is a major high-energy carrier for future energy technologies, if produced from renewable electrical energy. Hydrogenase enzymes offer a pathway for bioelectrochemically producing hydrogen that is advantageous over traditional platforms for hydrogen production because of low overpotentials and ambient operating temperature and pressure. However, electron delivery from the electrode surface to the enzyme's active site is often rate-limiting. Here, it is shown that three different hydrogenases from Clostridium pasteurianum and Methanococcus maripaludis, when immobilized at a cathode in a cobaltocene-functionalized polyallylamine (Cc-PAA) redox polymer, mediate rapid and efficient hydrogen evolution. Furthermore, it is shown that Cc-PAA-mediated hydrogenases can operate at high faradaic efficiency (80-100 %) and low apparent overpotential (-0.578 to -0.593 V vs. SHE). Specific activities of these hydrogenases in the electrosynthetic Cc-PAA assay were comparable to their respective activities in traditional methyl viologen assays, indicating that Cc-PAA mediates electron transfer at high rates, to most of the embedded enzymes.


Assuntos
Hidrogéis/química , Hidrogênio/química , Hidrogenase/química , Paraquat/química , Polímeros/metabolismo , Domínio Catalítico , Clostridium/enzimologia , Eletrodos , Elétrons , Oxirredução
10.
J Mol Biol ; 432(7): 2164-2185, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32087202

RESUMO

The human guanylate-binding protein 1 (hGBP1) belongs to the dynamin superfamily proteins and represents a key player in the innate immune response. Farnesylation at the C-terminus is required for hGBP1's activity against microbial pathogens, as well as for its antiproliferative and antitumor activity. The farnesylated hGBP1 (hGBP1fn) retains many characteristics of the extensively studied nonfarnesylated protein and gains additional abilities like binding to lipid membranes and formation of hGBP1fn polymers. These polymers are believed to serve as a protein depot, making the enzyme immediately available to fight the invasion of intracellular pathogens. Here we study the molecular mechanism of hGBP1 polymer formation as it is a crucial state of this enzyme, allowing for a rapid response demanded by the biological function. We employ Förster resonance energy transfer in order to trace intra and intermolecular distance changes of protein domains. Light scattering techniques yield deep insights into the changes in size and shape. The GTP hydrolysis driven cycling between a closed, farnesyl moiety hidden state and an opened, farnesyl moiety exposed state represents the first phase, preparing the molecule for polymerization. Within the second phase of polymer growth, opened hGBP1 molecules can be incorporated in the growing polymer where the opened structure is stabilized, similar to a surfactant molecule in a micelle, pointing the farnesyl moieties into the hydrophobic center and positioning the head groups at the periphery of the polymer. We contribute the molecular mechanism of polymer formation, paving the ground for a detailed understanding of hGBP1 function.


Assuntos
Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Guanosina Trifosfato/metabolismo , Polímeros/química , Polímeros/metabolismo , Sítios de Ligação , Células HeLa , Humanos , Hidrólise , Cinética , Prenilação , Ligação Proteica , Conformação Proteica , Multimerização Proteica
11.
Carbohydr Polym ; 232: 115822, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952617

RESUMO

Chondroitin sulfate is a linear glycosaminoglycan widely distributed as an important extracellular matrix component of mammalian cells. It participates in numerous pathological processes, however, illustration of its diverse biological roles is hampered by the unavailability of structurally defined chondroitin polymers and their derivatives. Herein, we report a novel homogeneous chondroitin polymers synthetic strategy which combines stepwise oligosaccharides synthesis with one-pot homogeneous chondroitin chain polymerization. Exogenous trisaccharide was proved to be the necessary acceptor for PmCS-catalyzed homogeneous chondroitin polymers synthetic reactions. The strategy exhibited a well-controlled relationship between the final sugar chain length and the molar ratios of reaction substrates that could synthesize homogenous chondroitin polymers with unprecedented narrow molecular weight distribution. More importantly, the strategy was further expanded to synthesis of unnatural zwitterionic and N-sulfonated chondroitin polymers by incorporation of sugar nucleotide derivatives into the synthetic approach.


Assuntos
Condroitina/biossíntese , N-Acetilgalactosaminiltransferases/metabolismo , Polímeros/metabolismo , Configuração de Carboidratos , Condroitina/análogos & derivados , Condroitina/química , Pasteurella multocida/enzimologia , Polimerização , Polímeros/química
12.
AAPS PharmSciTech ; 21(3): 78, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970547

RESUMO

Protein drugs were considered to be the first choice to treat many human diseases, but their clinical application was usually limited by their short half-life and lack of validated targeted therapy. Here, a series of folate-functionalized poly(ethylene glycol)-b-(poly(2-aminoethyl-L-glutamate)-g-poly(L-glutamic acid))s (FA-PEG-b-(PELG-g-PLGA)s) were designed as tumor-targeted carriers for cationic protein delivery. Compared with traditional copolymers consisting of PEG and linear charged hydrophilic blocks, FA-PEG-b-(PELG-g-PLGA) with brush-like polyelectrolyte segments were beneficial to improving their electrostatic interactions with loading protein molecules, thus increasing drug-loading stability and protecting encapsulated proteins from degradation. The designed polymer brushes could efficiently encapsulate cytochrome C (CytC), a cationic model protein, to form polyion complex (PIC) micelles with an average particle size of approximately 200 nm. An in vitro drug release study showed that the drug-loading stability of the formed PIC micelles was largely improved. The functionalization of the block copolymer carriers with a targeting folate group enhanced the tumor cell growth inhibition and total apoptotic rates induced by CytC. Our results shed light on the unique advantages of brush-like polymer carriers in delivering cationic proteins, and the poly(L-glutamic acid)-based linear-brush diblock copolymers could be applied as a versatile delivery platform for molecular targeting in cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ácido Glutâmico/síntese química , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Proteínas/síntese química , Animais , Cátions , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/metabolismo , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Células NIH 3T3 , Tamanho da Partícula , Poliésteres/administração & dosagem , Poliésteres/metabolismo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/metabolismo , Proteínas/administração & dosagem , Proteínas/metabolismo
13.
Clin Hemorheol Microcirc ; 75(2): 163-176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929151

RESUMO

Copolyetheresterurethane (PDC) is a biodegradable, shape-memory biomaterial, which has been shown to be of low toxicity and pro-angiogenic in vitro. In the present study we examined the in vivo compatibility of PDC as a compression molded film and as electrospun scaffolds and its well established constituent, the homopolymer poly(p-dioxanone) (PPDO), which were compared with the clinically used poly[(vinylidene fluoride)-co-hexafluoropropene] (PVDF) as reference material. The materials were implanted in the subcutaneous tissue of mice and the host responses were analyzed histologically 7 and 28 days after implantation.All materials induced a foreign body response (FRB) including the induction of foreign body giant cells and a peripheral fibrous capsule. PDC, PPDO and PVDF films showed no signs of degradation after 28 days. PDC films showed a significantly reduced associated macrophage layer and fibrous capsule on their surface. Few fragments of PDC and PPDO scaffolds were present at the implantation site, while PVDF scaffolds were still present in large amounts at day 28. Especially aligned electrospun PDC scaffold induced a significantly thinner fibrous and a slightly reduced inflammatory response after 28 days of implantation. In addition, only PDC aligned fibrous scaffold structures induced a significant increase in angiogenesis.In summary, PDC films outperformed PPDO and PVDF films in terms of compatibility, especially in capsule and macrophage layer thickness. Through microstructuring of PDC and PPDO into scaffolds an almost complete degradation was observed after 28 days, while their respective films remained almost unchanged. However, the capsule thickness of all scaffolds was comparable to the films after 28 days. Finally, the parallel arrangement of PDC fibers enabled a strong enhancement of angiogenesis within the scaffold. Hence, material chemistries influence overall compatibility in vivo, while angiogenesis could be influenced more strongly by microstructural parameters than chemical ones.


Assuntos
Materiais Biocompatíveis/química , Polímeros/metabolismo , Engenharia Tecidual/métodos , Animais , Masculino , Camundongos
14.
Clin Hemorheol Microcirc ; 75(2): 201-217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31985458

RESUMO

Implantation of synthetic small-diameter vascular bypass grafts is often associated with an increased risk of failure, due to thrombotic events or late intimal hyperplasia. As one of the causes an insufficient hemocompatibility of the artificial surface is discussed. Endothelialization of synthetic grafts is reported to be a promising strategy for creating a self-renewing and regulative anti-thrombotic graft surface. However, the establishment of a shear resistant cell monolayer is still challenging. In our study, cyto- and immuno-compatible poly(ether imide) (PEI) films were explored as potential biomaterial for cardiovascular applications. Recently, we reported that the initial adherence of primary human umbilical vein endothelial cells (HUVEC) was delayed on PEI-films and about 9 days were needed to establish a confluent and almost shear resistant HUVEC monolayer. To accelerate the initial adherence of HUVEC, the PEI-film surface was functionalized with an aptamer-cRGD peptide based endothelialization supporting system. With this functionalization the initial adherence as well as the shear resistance of HUVEC on PEI-films was considerable improved compared to the unmodified polymer surface. The in vitro results confirm the general applicability of aptamers for an efficient functionalization of substrate surfaces.


Assuntos
Aptâmeros de Peptídeos/metabolismo , Éter/metabolismo , Imidas/metabolismo , Polímeros/metabolismo , Técnicas de Cultura de Células , Humanos
15.
J Fluoresc ; 30(1): 157-174, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31970584

RESUMO

Enzymatic polymerization of 2,6-diaminopyridine (DAP) compound in the presence of HRP (Horse radish peroxidase) and H2O2 (hydrogen peroxide) with Poly(DAP-en) with the structures of two different types of polymers obtained by the oxidative polymerization of Poly(DAP-ox) using H2O2 in an aqueous basic environment was illuminated by 1H-NMR, 13C-NMR, FT-IR, UV-Vis spectral methods. GPC (gel permeation chromatography), TGA (thermal gravimetric analysis), DSC (differential scanning calorimetry), CV (cyclic voltammetry), fluorescence analysis and conductivity measurements to characterize the compounds and their electronic structure were examined. SEM analyzes were performed for the morphological properties of the compounds. As a result of the analysis, it was observed that the polymer obtained by enzymatic polymerization was better than the polymer obtained by oxidative method. It was observed that the results of the fluorescence measurements were better than Poly(DAP-en) in Poly(DAP-ox) emitting blue and green light. According to TGA analysis, the first decay temperatures for Poly (DAP-en) and Poly (DAP-ox) were calculated as 342 °C and 181 °C, respectively. The higher value of glass transition temperature for poly (DAP-en) confirms that the average molar mass is higher than 8650 Da for Poly (DAP-en) according to GPC analysis.


Assuntos
Peroxidase do Rábano Silvestre/metabolismo , Piridinas , Condutividade Elétrica , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Estrutura Molecular , Oxirredução , Polimerização , Polímeros/química , Polímeros/metabolismo , Piridinas/análise , Piridinas/síntese química , Piridinas/metabolismo , Solubilidade , Espectrometria de Fluorescência , Temperatura
16.
Proc Natl Acad Sci U S A ; 117(6): 2770-2778, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31988132

RESUMO

Organelle-specific nanocarriers (NCs) are highly sought after for delivering therapeutic agents into the cell nucleus. This necessitates nucleocytoplasmic transport (NCT) to bypass nuclear pore complexes (NPCs). However, little is known as to how comparably large NCs infiltrate this vital intracellular barrier to enter the nuclear interior. Here, we developed nuclear localization signal (NLS)-conjugated polymersome nanocarriers (NLS-NCs) and studied the NCT mechanism underlying their selective nuclear uptake. Detailed chemical, biophysical, and cellular analyses show that karyopherin receptors are required to authenticate, bind, and escort NLS-NCs through NPCs while Ran guanosine triphosphate (RanGTP) promotes their release from NPCs into the nuclear interior. Ultrastructural analysis by regressive staining transmission electron microscopy further resolves the NLS-NCs on transit in NPCs and inside the nucleus. By elucidating their ability to utilize NCT, these findings demonstrate the efficacy of polymersomes to deliver encapsulated payloads directly into cell nuclei.


Assuntos
Núcleo Celular/metabolismo , Nanopartículas/química , Polímeros/química , Transporte Ativo do Núcleo Celular , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Núcleo Celular/genética , Sistemas de Liberação de Medicamentos , Guanosina Trifosfato/metabolismo , Células HeLa , Humanos , Carioferinas , Nanopartículas/metabolismo , Sinais de Localização Nuclear/química , Sinais de Localização Nuclear/metabolismo , Poro Nuclear/metabolismo , Polímeros/metabolismo
17.
Biomater Sci ; 8(1): 290-301, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31696871

RESUMO

The performance of non-viral gene delivery vehicles, especially cationic polymers, is often challenged by the multiple cellular barriers that pose inconsistent requirements for material properties. A most pronounced inconsistency is exemplified by the molecular weight (MW)-related transfection efficiency and cytotoxicity. In this study, we report the development of photo-degradable, branched poly(ß-amino ester)s (BPAE-NB) to realize efficient and photo-controlled DNA and siRNA delivery. BPAE-NB possessing built-in light-responsive 2-nitrobenzene moieties in the polymer backbone was synthesized via the A2 (amine) + B3 (triacrylate) + C2 (diacrylate) polycondensation reaction from 4-amino-1-butanol (A2), trimethylolpropane triacrylate (B3), and (2-nitro-1,3-phenylene)bis(methylene) diacrylate (NPBMDA, C2). The highly branched BPAE-NB with the multivalent arrangement of cationic groups provides stronger nucleic acid binding capacity than its linear analogue LPAE-NB, and thus features stronger trans-membrane gene delivery capabilities and higher transfection efficiencies. Upon UV light irradiation, the backbone of BPAE-NB can quickly degrade into low-MW fragments as a consequence of the cleavage of the light-responsive 2-nitrobenzene, thus promoting intracellular gene release and diminishing the toxicity of materials at the post-transfection state. As such, in multiple mammalian cells, BPAE-NB exhibited remarkably higher DNA/siRNA transfection efficiency yet lower cytotoxicity than its non-responsive analogue BPAE-CC upon light irradiation, notably outperforming commercial reagents PEI 25k and Lipofectamine 2000. This study therefore provides an effective topology- and photo-controlled approach to precisely manipulate the transfection efficiency and toxicity of polycationic gene vectors, and may also provide promising additions to the existing non-viral gene delivery vectors.


Assuntos
DNA/metabolismo , Polímeros/química , RNA Interferente Pequeno/metabolismo , Transfecção/métodos , Raios Ultravioleta , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , DNA/química , Humanos , Cinética , Camundongos , Polímeros/metabolismo , Polímeros/toxicidade , Interferência de RNA , RNA Interferente Pequeno/química , Survivina/antagonistas & inibidores , Survivina/genética , Survivina/metabolismo
18.
Food Chem ; 305: 125459, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520919

RESUMO

In this study the elemental compositions of melanoidin formed at 160 °C from d-glucose (Glc) and l-alanine (Ala) as well as from fructosylalanine - the corresponding Amadori rearrangement product - were compared. Specific chemical bonds were probed by FTIR spectroscopy. This approach tackles the different chemical pathways for melanoidin formation via the Amadori rearrangement in contrast to the reaction from Glc/Ala. Melanoidins formed from fructosylalanine contain about twice as much nitrogen and therefore amino acid as compared to melanoidin from Glc/Ala and exhibit higher absorption in the UV/Vis. Consequently, melanoidins formed from Glc/Ala contain more sugar degradation products with lower absorption due to a smaller size of the conjugated double bond network.


Assuntos
Alanina/análogos & derivados , Alanina/química , Frutose/análogos & derivados , Frutose/química , Glucose/química , Polímeros/química , Frutose/síntese química , Espectroscopia de Ressonância Magnética , Reação de Maillard , Polímeros/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
19.
Environ Pollut ; 259: 113836, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31887586

RESUMO

The perdurability of plastics in the environment is one of the major concerns of plastic pollution and, as a consequence, oceans are accumulating large amounts of plastic. The degradation of conventional and biobased materials was evaluated through a laboratory experiment for a year simulating four different conditions in the marine environment. The water column environmental compartment was simulated under euphotic and aphotic (with and without light availability) conditions. The seafloor environmental compartment was simulated with sediment under non-polluted and polluted conditions. By combining weight loss (%), spectroscopic and thermal analyses, the degradation patterns regarding the polymer structure were assessed. The studied biobased materials were polylactic acid (PLA) based materials and showed higher degradability than conventional ones. The weight loss of conventional materials was not influenced by the water column or sediment, while in PLA-based materials, the degradation rates were ca. 5 times greater in the sediment than in the water column. The absorbance (Abs) value at 3400 cm-1 for polyethylene terephthalate (PET), and carbonyl (CO) index for PET and PLA could be useful to detect early signs of degradation. The crystallization index could be a useful parameter to discriminate degradation stages. The obtained results highlight the different degradability rates of materials depending on the specific environmental marine conditions.


Assuntos
Plásticos , Polímeros , Poluentes Químicos da Água , Monitoramento Ambiental , Oceanos e Mares , Plásticos/metabolismo , Polietilenotereftalatos/análise , Polímeros/metabolismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo
20.
Curr Opin Gastroenterol ; 36(2): 147-154, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31850930

RESUMO

PURPOSE OF REVIEW: Fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) dietary restriction ameliorates irritable bowel syndrome (IBS) symptoms; however, not all individuals with IBS respond. Given the gut microbiome's role in carbohydrate fermentation, investigators have evaluated whether the gut microbiome may predict low FODMAP diet efficacy. RECENT FINDINGS: Gut microbiome fermentation, even to the same carbohydrate, is not uniform across all individuals with several factors (e.g. composition) playing a role. In both children and adults with IBS, studies are emerging suggesting the gut microbiome may predict low FODMAP diet efficacy. However, there is significant heterogeneity in the approaches (study population, microbiome assessment methods, statistical techniques, etc.) used amongst these studies. SUMMARY: The gut microbiome holds promise as a predictor of low FODMAP diet efficacy. However, further investigation using standardized approaches to evaluate the microbiome while concomitantly assessing other potential predictors are needed to more rigorously evaluate this area.


Assuntos
Dieta com Restrição de Carboidratos/métodos , Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/dietoterapia , Monossacarídeos/administração & dosagem , Oligossacarídeos/administração & dosagem , Polímeros/administração & dosagem , Dissacarídeos/administração & dosagem , Dissacarídeos/metabolismo , Fermentação , Gastroenteropatias/dietoterapia , Gastroenteropatias/metabolismo , Gastroenteropatias/fisiopatologia , Humanos , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Monossacarídeos/metabolismo , Oligossacarídeos/metabolismo , Polímeros/metabolismo , Resultado do Tratamento
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