RESUMO
The bottom-up constructed artificial cells help to understand the cell working mechanism and provide the evolution clues for organisms. The energy supply and metabolism mimicry are the key issues in the field of artificial cells. Herein, an artificial cell containing cyanobacteria capable of light harvesting and carbon dioxide fixation is demonstrated to produce glucose molecules by converting light energy into chemical energy. Two downstream "metabolic" pathways starting from glucose molecules are investigated. One involves enzyme cascade reaction to produce H2 O2 (assisted by glucose oxidase) first, followed by converting Amplex red to resorufin (assisted by horseradish peroxidase). The other pathway is more biologically relevant. Glucose molecules are dehydrogenated to transfer hydrogens to nicotinamide adenine dinucleotide (NAD+ ) for the production of nicotinamide adenine dinucleotide hydride (NADH) molecules in the presence of glucose dehydrogenase. Further, NADH molecules are oxidized into NAD+ by pyruvate catalyzed by lactate dehydrogenase, meanwhile, lactate is obtained. Therefore, the cascade cycling of NADH/NAD+ is built. The artificial cells built here pave the way for investigating more complicated energy-supplied metabolism inside artificial cells.
Assuntos
Células Artificiais , Cianobactérias , NAD/química , Dióxido de Carbono , Ácido Láctico , Glucose , Cianobactérias/metabolismo , OxirreduçãoRESUMO
Polarity determines the oil resistance property of elastomers. In this work, three bio-based polyester elastomers (BPEs) with different mass fraction of ester groups (E) are designed and synthesized aiming to study the relationship of E and oil resistance performance, and to obtain bio-based elastomer materials with tunable oil resistance. Through adjusting the chain length of monomers, E of poly(ethylene glycol/1,3-propanediol/succinate/adipate/itaconate)(PEPSAI), poly(1,3-propanediol/1,4-butanediol/succinate/adipate/itaconate)(PPBSAI), and poly(1,3-propanediol/1,4-butanediol/sebacate/adipate/itaconate)(PPBSeAI) are ≈50.39%, 48.55%, and 39.68%, respectively. Results show that E has great influence on the oil resistance of BPEs. After being immersed in IRM-903# oil for 72 h at room temperature, the changes in mass and volume of BPEs decrease along with the increasing mass fraction of ester groups, indicating improved oil resistance performance. PEPSAI with the highest mass fraction of ester groups presents better oil resistance and lower Tg (better low-temperature resistance) than one of the most used commercial oil-resistant rubber nitrile rubber (N230S). Thus, this work provides a promising strategy to obtain bio-based oil resistant elastomers with practical value.
Assuntos
Elastômeros , Poliésteres , Borracha , Succinatos , ÉsteresRESUMO
Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.
Assuntos
Flavonoides , Psoralea , Humanos , Proteína X Associada a bcl-2 , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Fabaceae/química , Flavonoides/química , Flavonoides/farmacologia , Frutas/química , Células MCF-7/efeitos dos fármacos , Células MCF-7/metabolismo , Polímeros , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Psoralea/químicaRESUMO
There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1ß, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis.
Assuntos
Perda do Osso Alveolar , Periodontite , Camundongos , Animais , NF-kappa B/metabolismo , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Microtomografia por Raio-X , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Osteoclastos/metabolismo , Periodontite/tratamento farmacológico , Periodontite/etiologia , Periodontite/metabolismo , Citocinas/metabolismo , Ligante RANK/metabolismoRESUMO
Cellulose aerogels are highly attractive candidates in various applications, such as thermal insulation, adsorption separation, biomedical field, and as carriers, due to their intrinsic merits of low density, high porosity, biodegradability, and renewability. However, the expensive cost of the supercritical drying process and poor mechanical properties limit their practical applications. Herein, a new method was presented to fabricate cellulose acetate/benzoxazine hybrid aerogels (CBAs) with low cost, low drying shrinkage, excellent mechanical properties under cryogenic condition (-196 °C), outstanding thermal insulation, flame retardancy, and good thermal stability by ambient pressure drying. In more detail, the weighted drying shrinkage rate of CBAs-T2 can be controlled to 6.8% (the average value along the radial and axial directions), mainly due to the enhanced skeleton, by introducing polybenzoxazine networking chains. The resultant CBAs-T2 exhibit outstanding mechanical properties at room temperature because of the presence of the polybenzoxazine hybrid in the cellulose networking system. CBAs-T2 still have good mechanical properties even after subjecting them to liquid nitrogen treatment. In addition, the optimal value of thermal conductivity (0.033 W m-1 K-1) is gained easily because of the uniform cross-linking networking structure and small pore size. A superior flame retardance of CBAs-T2 is endowed to achieve self-extinguishment after ignition, which is attributed to the presence of the aromatic ring in the backbone structure. Moreover, the good thermal stability of CBAs-T2 is attributed to the fact that polybenzoxazine components could resist the decomposition of cellulose acetate and inhibit heat release during the combustion process. Our study would provide a novel method for obtaining biomass aerogels including the cellulose-based materials system with low drying shrinkage and superior mechanical properties despite bearing a cryogenic environment by the low-cost ambient pressure drying approach.
Assuntos
Benzoxazinas , Celulose , Celulose/química , Temperatura , PorosidadeRESUMO
BACKGROUND AND AIMS: The early growth response 2 gene (EGR2) mutations are associated with a group of hereditary neuropathy, including axonal neuropathy and hypomyelinating neuropathy or Charcot-Marie-Tooth disease (CMT) type 1D. We aim to perform an electrodiagnostic, nerve imaging, and histological study of EGR2-associated neuropathy. MATERIALS AND METHODS: We performed a retrospective analysis of two patients with EGR2-related neurology at our hospital. The neuropathy was confirmed by the nerve conduction study. Nerve imaging and sural biopsies were performed in two patients. RESULTS: Two unrelated boys exhibited early-onset length-dependent neuropathy. Next generation sequencing identified EGR2 gene with previously described E412K mutation in the third zine finger domain in patient 1 and a previously undescribed variant D355N mutation in the first zinc finger domain in patient 2. The magnetic resonance imaging of the lumbosacral plexus showed no abnormalities in patient 1 and thickened lumbosacral plexuses in patient 2. Electrophysiology and nerve biopsies showed a prominent axonal neuropathy, accompanied with demyelinating involvement. CONCLUSION: Therefore, it seemed that the EGR2 mutations could cause not only the known demyelinating type and axonal type but also mixed-type CMT. Our findings expanded the phenotypic heterogeneities of EGR2-associated neuropathy.
Assuntos
Doença de Charcot-Marie-Tooth , Masculino , Humanos , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Estudos Retrospectivos , Fenótipo , Axônios/patologia , Mutação , Nervo Sural/patologia , Proteína 2 de Resposta de Crescimento Precoce/genéticaRESUMO
Frontal polymerization provides a rapid, economic, and environmentally friendly methodology to manufacture thermoset polymers and composites. Despite its efficiency and reduced environmental impact, the manufacturing method is underutilized due to the limited fundamental understanding of its dynamic control. This work reports the control and patterning of the front propagation in a dicyclopentadiene resin by immersion of phase-changing polycaprolactone particles. Predictive and designed patterning is enabled by multiphysical numerical analyses, which reveal that the interplay between endothermic phase transition, exothermic chemical reaction, and heat exchange govern the temperature, velocity, and propagation path of the front via two different interaction regimes. To pattern the front, one can vary the size and spacing between the particles and increase the number of propagating fronts, resulting in tunable physical patterns formed due to front separation and merging near the particles. Both single- and double-frontal polymerization experiments in an open mold are performed. The results confirm the front-particle interaction mechanisms and the shapes of the patterns explored numerically. The present study offers a fundamental understanding of frontal polymerization in the presence of heat-absorbing second-phase materials and proposes a potential one-step manufacturing method for precisely patterned polymeric and composite materials without masks, molds, or printers.
Assuntos
Polímeros , Transição de Fase , Polimerização , TemperaturaRESUMO
Precise polymer architecture and self-assembled morphological control are attractive due to their promising applications, such as drug delivery, biosensors, tissue engineering and "smart" optical systems. Herein, starting from the same hydrophilic units poly(ethylene glycol) (PEG), using CO2 -sensitive monomer N, N-diethylaminoethyl methacrylate (DEAEMA) and hydrophobic monomer benzyl methacrylate (BzMA), a series of well-defined statistical, block, and gradient copolymers is designed and synthesized with similar degree of polymerization but different monomer sequences by batch and semi-batch RAFT polymerization process and their CO2 -responsive behaviors of these nano-objects is systematically studied. The gradient copolymers are generated by using semi-batch methods with programmed monomer feed rate controlled by syringe pumps, achieving precise control over desired gradient copolymer composition distribution. In aqueous solution, the copolymers could self-assemble into various aggregates before CO2 stimulus. Upon bubbling CO2 , the gradient copolymers preferred to form nanosheet-like structures, while the block and statistical copolymers with similar molar mass could only form larger vesicles with thinner membrane thickness or disassemble. The semi-batch strategy to precisely control over the desired composition distribution of the gradient segment presents an emerging trend for the fabrication and application of stimuli-responsive polymers.
Assuntos
Dióxido de Carbono , Micelas , Polietilenoglicóis , Polimerização , PolímerosRESUMO
Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis. PF-3845 significantly suppressed osteoclast differentiation and decreased the induction of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific markers. Actin ring formation and osteoclastic bone resorption were also reduced by PF-3845, and the anti-osteoclastogenic and anti-resorptive activities were mediated by the suppression of phosphorylation of rapidly accelerated fibrosarcoma (RAF), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase, (ERK) and nuclear factor κB (NF-κB) inhibitor (IκBα). Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Amidoidrolases/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Periodontite/tratamento farmacológico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Animais , Reabsorção Óssea/tratamento farmacológico , Células Cultivadas , Modelos Animais de Doenças , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Resultado do TratamentoRESUMO
Phospholipid self-assemblies are ubiquitous in organisms. Nonspherical lipid-based proto-organelles bear the merits with structures similar to real organelles. It is still a challenge to mimic mass transport between organelles inside cells. Herein, unusual phospholipid self-assemblies shaped like ancient Chinese coins (ACC) were discovered by the recrystallization of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in an ethanol/water solution from 50 to 25 °C with a certain cooling rate. Their diameter and the ratio of the square edge to the disk diameter were controlled by varying ethanol percentage, lipid concentration, and cooling rate. The ACC-shaped phospholipid bicelles expanded to stacked cisterna structures in pure water, which were regarded as artificial organelles. Mass transport among organelles in a cell was mimicked via the membrane fusion of vesicle shuttles and artificial organelles, which induced cascade enzyme reactions inside artificial organelles. The ACC-shaped phospholipid assemblies provide nice platforms for the studies of cell biology and bottom-up synthetic biology.
Assuntos
Fosfolipídeos/química , Imagem Óptica , Fosfolipídeos/síntese química , Lipossomas Unilamelares/químicaRESUMO
Photodynamic therapy (PDT) is commonly employed in clinics to treat the cancer, but because of the hypoxic tumor microenvironment prevalent inside tumors, PDT therapeutic efficiency is not adequate hence limiting the effectiveness of PDT. Therefore, we designed a nanocomposite consisting of reduced nanographene oxide (rGO) modified with polyethylene glycol (PEG), manganese dioxide (MnO2), upconversion nanoparticles (UCNPs), and Chlorin e6 (Ce6) to spark oxygen production from H2O2 with the aim of relieving the tumor hypoxic microenvironments. For in vivo tumor PDT and photothermal therapy (PTT), UCNPs-Ce6-labeled rGO-MnO2-PEG nanocomposites were used as a therapeutic agent, augmenting the therapeutic efficiency of PDT via redox progression through the catalytic H2O2 decomposition pathway and further achieving excellent tumor inhibition. It is important to mention that degradation of MnO2 in an acidic cellular microenvironment leads to the creation of a massive volume of Mn2+ which was employed as a contrast mediator for magnetic resonance imaging (MRI). Our research postulates an approach to spark O2 formation through an internal stimulus to augment the efficiency of MRI- and computerized tomography (CT)-imaging-guided PDT and PTT.
Assuntos
Antineoplásicos/uso terapêutico , Nanocompostos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Clorofilídeos , Feminino , Fluoretos/química , Fluoretos/efeitos da radiação , Fluoretos/uso terapêutico , Gadolínio/química , Gadolínio/efeitos da radiação , Gadolínio/uso terapêutico , Grafite/química , Grafite/uso terapêutico , Humanos , Raios Infravermelhos , Compostos de Manganês/química , Compostos de Manganês/uso terapêutico , Camundongos , Nanocompostos/química , Nanopartículas/química , Óxidos/química , Óxidos/uso terapêutico , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Porfirinas/química , Porfirinas/efeitos da radiação , Microambiente Tumoral/fisiologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Oxy-combustion is one of the most promising technologies for carbon capture and sequestration. When CO2-neutral biomass is burned under oxy-combustion conditions, named "oxy-biomass combustion" a negative CO2 emission can be achieved. However, the high content of potassium and chlorine in biomass results in sever ash deposition and corrosion in air fired furnaces, which are further aggravated in oxy-combustion mode due to the enrichment of corrosive species by flue gas recycle. In this paper, the hot corrosion behaviors and mechanism of two representative materials (TP347H, HR3C) used for superheaters in furnaces are studied. The effects of oxy-combustion atmosphere, KCl deposition, effect of SO2, effect of water vapor, and temperature on the corrosion kinetics at the starting stage are investigated. The corrosion severity of the materials was determined using the weight gain method, and the microstructures and chemical compositions of corrosion layers were characterized by the scanning electron microscopy with energy dispersive spectroscopy, and X-ray diffraction. The results show that the hot corrosion rate is significantly sped up by KCl deposition, more than five times the gas corrosion rate under the same gas composition and temperature. HR3C with higher Cr and Ni contents is more likely to form Cr enrichment on the interface between the corrosion layer and the substrate than TP347H, resulting in stronger resistance to the hot corrosion than TP347H. When the corrosion atmosphere is changed from air-combustion to oxy-combustion, the hot corrosion rate is reduced with a denser Cr oxide film and less metal sulfides. The increase of temperature in the presence of KCl deposition significantly affects the hot corrosion rate, e.g. the corrosion rate at 650 °C is 16 times higher than that at 450 °C. Water vapor and SO2 concentrations have opposite influences on the hot corrosion, respectively. Compared to the dry environment, a high-humidity environment decreases the hot corrosion rate; however, a higher SO2 concentration facilitates the sulfation of KCl deposits, leading to stronger damage to the chromium oxide film and thereby an increased hot corrosion rate.
Assuntos
Atmosfera , Aço Inoxidável , Biomassa , Dióxido de Carbono , Corrosão , Temperatura AltaRESUMO
Targeting the spleen with nanoparticles could increase the efficacy of vaccines and cancer immunotherapy, and have the potential to treat intracellular infections including leishmaniasis, trypanosome, splenic TB, AIDS, malaria, and hematological disorders. Although, nanoparticle capture in both the liver and spleen has been well documented, there are only a few examples of specific capture in the spleen alone. It is proposed that the larger the nanoparticle size (>400 nm) the greater the specificity and capture within the spleen. Here, we synthesized five nanostructures with different shapes (ranging from spheres, worms, rods, nanorattles, and toroids) and poly( N-isopropylacrylamide), PNIPAM, surface coating using the temperature-directed morphology transformation (TDMT) method. Globular PNIPAM (i.e., water insoluble) surface coatings have been shown to significantly increase cell uptake and enhanced enzyme activity. We incorporated a globular component of PNIPAM on the nanostructure surface and examined the in vivo biodistribution of these nanostructures and accumulation in various tissues and organs in a mouse model. The in vivo biodistribution as a function of time was influenced by the shape and PNIPAM surface composition, in which organ capture and retention was the highest in the spleen. The rods (â¼150 nm in length and 15 nm in width) showed the highest capture and retention of greater than 35% to the initial injection amount compared to all other nanostructures. It was found that the rods specifically targeted the cells in the red pulp region of the spleen due to the shape and PNIPAM coating of the rod. This remarkable accumulation and selectively into the spleen represents new nanoparticle design parameters to develop new splenotropic effects for vaccines and other therapeutics.
Assuntos
Resinas Acrílicas/química , Nanopartículas/química , Animais , Feminino , Temperatura Alta , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/metabolismo , Nanopartículas/ultraestrutura , Células RAW 264.7 , Baço/metabolismo , Polímeros Responsivos a Estímulos/química , Distribuição TecidualRESUMO
In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.
Assuntos
Ácido Fólico/química , Neoplasias/patologia , Técnicas Fotoacústicas/métodos , Poloxâmero/química , Pontos Quânticos/química , Compostos de Prata/química , Células A549 , Morte Celular , Linhagem Celular Tumoral , Difusão Dinâmica da Luz , Células HeLa , Humanos , Óleos/química , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Pontos Quânticos/ultraestrutura , Solubilidade , Espectrofotometria Ultravioleta , Eletricidade EstáticaRESUMO
Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based cationic lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the steroid-based cationic lipids, average particle sizes, surface potentials, morphologies and stability of the steroid-based cationic lipids/pDNA lipoplexes were disclosed to depend largely on the steroid skeletons. Cellular evaluation results revealed that cytotoxicity and gene transfection efficiency of the steroid-based cationic lipids in H1299 and HeLa cells strongly relied on the steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis pathways, and an intracellular trafficking route of "lipid-raft-mediated endocytosisâlysosomeâcell nucleic localization" was accordingly proposed. The study provided possible approach for developing high-performance steroid-based lipid gene carriers, in which the cytotoxicity, gene transfection capability, endocytosis pathways, and intracellular trafficking/localization manners could be tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy, among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even under high serum concentration (50% fetal bovine serum), making it an efficient gene transfection agent for practical application.
Assuntos
Endocitose , Técnicas de Transferência de Genes , Lipossomos/metabolismo , Plasmídeos/metabolismo , Esteroides/química , Cavéolas/metabolismo , DNA/química , DNA/genética , Células HeLa , Humanos , Lipossomos/efeitos adversos , Lipossomos/química , Lisossomos/metabolismo , Microdomínios da Membrana/metabolismo , Plasmídeos/química , Plasmídeos/genéticaRESUMO
In this paper, we describe a method for the stabilization of low-boiling point (low-bp) perfluorocarbons (PFCs) at physiological temperatures by an amphiphilic triblock copolymer which can emulsify PFCs and be cross-linked. After UV-induced thiol-ene cross-linking, the core of the PFC emulsion remains in liquid form even at temperatures exceeding their boiling points. Critically, the formulation permits vaporization at rarefactional pressures relevant for clinical ultrasound.
Assuntos
Meios de Contraste/química , Fluorocarbonos/química , Nanopartículas/química , Polímeros/química , Ondas Ultrassônicas , Tamanho da Partícula , Temperatura , Raios Ultravioleta , VolatilizaçãoRESUMO
BACKGROUND To examine the effects of the addition of autologous platelet-rich plasma (PRP) into bilayer poly(lactide-co-glycolide) (PLGA) scaffolds on the reconstruction of osteochondral defects in a rabbit model. MATERIAL AND METHODS Porous PLGA scaffolds were prepared in a bilayered manner to reflect the structure of chondral and subchondral bone. Bone defects, measuring 4 mm in diameter and 4 mm in thickness, were created in both knee joints in 18 healthy New Zealand white rabbits, aged between 120-180 days old. Rabbits were randomly divided into three groups: rabbits with bone defects implanted with bilayer PLGA scaffolds (PLGA group) (N=6); or with bilayer PLGA and autologous PRP (PLGA/PRP group) (N=6); and the untreated group (control group) (N=6). The gross morphology, histology, and immunohistochemistry for the expression of collagen type II and aggrecan were observed at 12 weeks after surgery and compared using a scoring system. Micro-computed tomography (CT) imaging and relative expression of specific genes were also assessed. RESULTS The platelet concentrations in the PRP samples were found to be 4.9 times greater than that of whole blood samples. The total score on gross appearance and histology was greatest in the PLGA/PRP group, as was the expression of collagen II and aggrecan of the neo-tissue. Micro-CT imaging showed that more subchondral bone was formed in the PLGA/PRP group. CONCLUSIONS Bilayer PLGA scaffolds loaded with autologous PRP improve the reconstruction of osteochondral defects in the rabbit model.
Assuntos
Articulações/patologia , Plasma Rico em Plaquetas/metabolismo , Poliglactina 910/química , Alicerces Teciduais/química , Cicatrização , Animais , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Imageamento Tridimensional , Imuno-Histoquímica , Articulações/diagnóstico por imagem , Articulações/cirurgia , Coelhos , Coloração e Rotulagem , Microtomografia por Raio-XRESUMO
Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement.
Assuntos
Catecóis/química , Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Polímeros/química , Células HeLa , Humanos , Fenômenos Magnéticos , Micelas , Nanopartículas/ultraestrutura , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
In this work, a series of diblock terpolymer poly(6-O-methacryloyl-D-galactopyranose)-b-poly(methacrylic acid-co-6-cholesteryloxy hexyl methacrylate) amphiphiles bearing attached galactose and cholesterol grafts denoted as the PMAgala-b-P(MAA-co-MAChol)s were designed and prepared, and these terpolymer amphiphiles were further exploited as a platform for intracellular doxorubicin (DOX) delivery. First, employing a sequential RAFT strategy with preliminarily synthesized poly(6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose) (PMAIpGP) macro-RAFT initiator and a successive trifluoroacetic acid (TFA)-mediated deprotection, a series of amphiphilic diblock terpolymer PMAgala-b-P(MAA-co-MAChol)s were prepared, and were further characterized by NMR, Fourier transform infrared spectrometer (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and a dynamic contact angle testing instrument (DCAT). In aqueous media, spontaneous micellization of the synthesized diblock terpolymer amphiphiles were continuously examined by critical micellization concentration assay, dynamic light scattering (DLS), and transmission electron microscopy (TEM), and the efficacies of DOX loading by these copolymer micelles were investigated along with the complexed nanoparticle stability. Furthermore, in vitro DOX release of the drug-loaded terpolymer micelles were studied at 37 °C in buffer under various pH conditions, and cell toxicities of as-synthesized diblock amphiphiles were examined by MTT assay. Finally, with H1299 cells, intracellular DOX delivery and localization by the block amphiphile vectors were investigated by invert fluorescence microscopy. As a result, it was revealed that the random copolymerization of MAA and MAChol comonomers in the second block limited the formation of cholesterol liquid-crystal phase and enhanced DOX loading efficiency and complex nanoparticle stability, that ionic interactions between the DOX and MAA comonomer could be exploited to trigger efficient DOX release under acidic condition, and that the diblock terpolymer micellular vector could alter the DOX trafficking in cells. Hence, these suggest the pH-sensitive PMAgala-b-P(MAA-co-MAChol)s might be further exploited as a smart nanoplatform toward efficient antitumor drug delivery.
Assuntos
Colesterol/química , Doxorrubicina/química , Galactose/química , Fosforilcolina/análogos & derivados , Polímeros/química , Ácidos Polimetacrílicos/química , Varredura Diferencial de Calorimetria/métodos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Micelas , Microscopia Eletrônica de Transmissão/métodos , Nanopartículas/química , Fosforilcolina/química , PolimerizaçãoRESUMO
Cellulose nanocrystals (CNCs) with different polymorphs CNC I and II were fabricated from native and mercerized microcrystalline cellulose (MCC) by sulfuric acid hydrolysis. CNC I and II were successfully acetylated by a "green" method, which was performed in an ionic liquid of 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4). X-ray diffraction (XRD) proved that the crystal structure of CNC I and II was maintained after acetylation. Transmission electron microscopy (TEM) showed the rod-like structure for acetylated CNC I and spherical crystal morphologies for acetylated CNC II. Thermogravimetric analysis (TGA) revealed that the thermal stability of CNC I and II was enhanced after acetylation. The effect of CNC polymorphs on the crystallization behavior and thermal stability of poly(lactic acid)/acetylated CNC (PLA/ACN) composites was investigated by differential scanning calorimetry (DSC) and TGA, respectively. It was found that compared to ACN I, ACN II was better able to promote the cold crystallization of PLA-based composites, and PLA/ ACN II possessed higher thermal stability.