RESUMEN
Given the advantages of antifouling capacity and good biocompatibility, zwitterionic polymers have been profoundly applied for drug delivery to improve the pharmacokinetics profile. Here, a zwitterionic polymer (poly (carboxybetaine methacrylate) (PCBMA)) nanogel was fabricated by one-step reflux precipitation polymerization for doxorubicin (DOX) loading. The obtained nanogels display favorable long blood circulation without priming immune responses as a result of the introduction of the zwitterionic group. Meanwhile, the disulfide bonds deriving from the crosslinker endow nanogels with excellent glutathione-responsive degradation and sufficient drug release under a reduction environment. The carboxylate groups originating from carboxybetaine provide modification sites to conjugate with fluorescent dye to achieve labeling and biodistribution tracking. Overall, under the significantly prolonging circulation and enhanced tumor accumulation through passive targeting, DOX-loaded PCBMA nanogels show a noticeable tumor inhibition effect in mouse colorectal cancer models, which may provide a delivery vehicle with great promise in cancer therapy.
Asunto(s)
Neoplasias , Polímeros , Animales , Ratones , Polímeros/química , Nanogeles , Distribución Tisular , Sistemas de Liberación de Medicamentos , Doxorrubicina , Neoplasias/tratamiento farmacológico , Portadores de Fármacos/químicaRESUMEN
3D printing of conductive polymers is an attractive technique for achieving high flexibility, wearability, and sensing characteristics without geometrical limitations. However, there is an urgent need to integrate printability, conductivity, and sensing capability. Herein, a conductive polymer ink for 3D printing that combines the desirable features of high electrical conductivity, flexible stretchability, and strain-sensing monitoring is prepared. The ink matrix is polydimethylsiloxane and synergistically enhanced by acetylene carbon black (ACB) and multi-walled carbon nanotubes (MWCNTs) (silane or un-silane-modified). The inks are screened step-by-step to explore their printability, rheology, mechanical properties, and electrical performance upon loading. The formation of an electrically conductive network, electrical properties upon tensile load, and strain sensing stability under cyclic stretching are investigated intensively. It is demonstrated that conductive polymers filled by ACB and silane-modified, MWCNTs (MWCNTs-MTES) possess superior printability, stretchability, conductivity, and strain sensing behaviors. Finally, a flexible wearable strain-sensing skin patch is printed, and it successfully records joint motion signals on human fingers, wrists, and elbows with good stability and repeatability. Those results show the extent of potential applications in healthcare and motion monitoring fields. This work provides an efficient and simple route to achieve comfortably wearable and high-performance strain sensors.
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Nanotubos de Carbono , Dispositivos Electrónicos Vestibles , Conductividad Eléctrica , Humanos , Polímeros , SilanosRESUMEN
BACKGROUND: There is a concern regarding the use of a closed-suction drain (CSD) in two-stage exchange arthroplasty for periprosthetic joint infection as it may decrease the antibiotic concentrations in the joint fluids. The purpose of this study was to identify whether the use of a CSD could reduce local antibiotic concentrations following spacer implantation. METHODS: A prospective, randomized, controlled trial was conducted at our institution between January 2018 and November 2018. We enrolled 32 patients undergoing two-stage exchange arthroplasty for periprosthetic hip infection with an interim cement spacer containing 4-g vancomycin and 2-g meropenem per 40-g methyl-methacrylate cement polymer. Patients were randomized and evenly divided into the study group (non-CSD) and control group (CSD group) by sealed envelopes. Drainage samples of joint fluids (n = 160) were collected every 24 h for the first five days following spacer implantation. The antibiotic concentrations of drainage samples were measured by high-performance liquid chromatography, and the bioactivities of the drainage samples against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) and E. coli were assessed. RESULTS: There was no significant difference in the decrease of vancomycin (study group vs. control group: 163.20 ± 77.05 vs. 162.39 ± 36.31; p = 0.917) and meropenem concentration (123.78 ± 21.04 vs. 117.27 ± 19.38; P = 0.548) between the two groups during the first five days following spacer implantation. All joint drainage samples in each group exhibited antibacterial activity against MSSA, MRSA and E. coli. CONCLUSIONS: The use of CSD following the implantation of an antibiotic-loaded cement spacer does not reduce the effectiveness of such a spacer in two-stage exchange arthroplasty. (Chinese Clinical Trial Registry, ChiCTR-INR-17014162. Registered 26 December 2017.).
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Antibacterianos/administración & dosificación , Artritis Infecciosa/cirugía , Artroplastia de Reemplazo de Cadera/métodos , Prótesis de Cadera/efectos adversos , Infecciones Relacionadas con Prótesis/cirugía , Anciano , Antibacterianos/química , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Cementos para Huesos/química , Femenino , Articulación de la Cadera/microbiología , Articulación de la Cadera/cirugía , Prótesis de Cadera/microbiología , Humanos , Masculino , Meropenem/administración & dosificación , Meropenem/química , Metilmetacrilato/química , Persona de Mediana Edad , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/prevención & control , Succión/efectos adversos , Succión/métodos , Resultado del Tratamiento , Vancomicina/administración & dosificación , Vancomicina/químicaRESUMEN
Cationic polyplex as commonly used nucleic acid carriers faced several shortcomings, such as high cytotoxicity, low serum stability, and slow cargo release at the target site. The traditional solution is covering a negative charged layer (e.g., hyaluronic acid, HA) via electrostatic interaction. However, it was far from satisfactory for the deshielding by physiological anions in circulation (e.g., serum proteins, phosphate). In this study, we proposed a new strategy of reversible covalent cross-linking to enhance stability in circulation and enable stimuli-disassembly of polyplexes in tumor cells. Here, 25k polyethylenimine (PEI) was chosen as model polycations for veriying the hypothesis. HA-PEI conjugation was formed by the cross-linking of adenosine triphosphate grafted HA (HA-ATP) with phenylboronic acid grafted PEI (PEI-PBA) via the chemical reaction between PBA and ATP. Compared with noncovalent polyplex by electrostatic interaction (HA/PEI), HA-PEI exhibited much better colloidal stability and serum stability. The covered HA-ATP layer on PEI-PBA could maintain stable in the absence of physiological anions, while HA layer on PEI in HA/PEI group showed obvious detachment after anion's competition. More importantly, the covalent cross-linking polyplex could selectively release siRNA in the ATP rich environment of cytosol and significantly improve siRNA silence. Besides, the covalent cross-linking with HA-ATP could effectively reduce the cytotoxicity of cationic polyplex, improve the uptake by B61F10 cells and promote the endosomal escape. Consequently, this strategy of HA-PEI conjugation significantly enhanced the siRNA transfection in the absence or presence of FBS (fetal bovine serum) on B16F10 cells and CHO cells. Taken together, the reversible covalent cross-linking approach shows obvious superiority compared with the noncovalent absorption strategy. It held great potential to be developed to polish up the performance of cationic polyplex on reducing the toxicity, enhancing the serum tolerance and achieving controlled release of siRNA at target site.
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Adenosina Trifosfato/química , Reactivos de Enlaces Cruzados/química , Técnicas de Transferencia de Gen , Poliaminas/química , Interferencia de ARN , Animales , Ácidos Borónicos/química , Células CHO , Línea Celular Tumoral , Cricetinae , Cricetulus , Ácido Hialurónico/química , Masculino , Ratones , Ratones Endogámicos C57BL , Polielectrolitos , Polietileneimina/química , Tratamiento con ARN de Interferencia/métodosRESUMEN
The ubiquitous occurrence of micro/nano plastics (MNPs) poses potential threats to ecosystem and human health that have attracted broad concerns in recent decades. Detection of MNPs in several remote regions has implicated atmospheric transport as an important pathway for global dissemination of MNPs and hence as a global health risk. In this review, the latest research progress on (1) sampling and detection; (2) origin and characteristics; and (3) transport and fate of atmospheric MNPs was summarized. Further, the current status of exposure risks and toxicological effects from inhaled atmospheric MNPs on human health is examined. Due to limitations in sampling and identification methodologies, the study of atmospheric nanoplastics is very limited today. The large spatial variation of atmospheric MNP concentrations reported worldwide makes it difficult to compare the overall indoor and outdoor exposure risks. Several in vitro, in vivo, and epidemiological studies demonstrate adverse effects of immune response, apoptosis and oxidative stress caused by MNP inhalation that may induce cardiovascular diseases and reproductive and developmental abnormalities. Given the emerging importance of atmospheric MNPs, the establishment of standardized sampling-pretreatment-detection protocols and comprehensive toxicological studies are critical to advance environmental and health risk assessments of atmospheric MNPs.
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Enfermedades Cardiovasculares , Ecosistema , Humanos , Microplásticos , Atmósfera , Apoptosis , PlásticosRESUMEN
Ferroptosis inhibits tumor growth by iron-dependently accumulating lipid peroxides (LPO) to a lethal extent, which can result from iron overload and glutathione peroxidase 4 (GPX4) inactivation. In this study, we developed biodegradable zwitterionic polymer-cloaked atorvastatin (ATV)-loaded ferric metal-organic frameworks (Fe-MOFs) for cancer treatment. Fe-MOFs served as nanoplatforms to co-deliver ferrous ions and ATV to cancer cells; the zwitterionic polymer membrane extended the circulation time of the nanoparticles and increased their accumulation at tumor sites. In cancer cells, the structure of the Fe-MOFs collapsed in the presence of glutathione (GSH), leading to the depletion of GSH and the release of ATV and Fe2+. The released ATV decreased mevalonate biosynthesis and GSH, resulting in GPX4 attenuation. A large number of reactive oxygen species were generated by the Fe2+-triggered Fenton reaction. This synergistic effect ultimately contributed to a lethal accumulation of LPO, causing cancer cell death. The findings both in vitro and in vivo suggested that this ferroptosis-inducing nanoplatform exhibited enhanced anticancer efficacy and preferable biocompatibility, which could provide a feasible strategy for anticancer therapy.
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Ferroptosis , Estructuras Metalorgánicas , Neoplasias , Humanos , Polímeros , Atorvastatina , Glutatión , Hierro , Peróxidos Lipídicos , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
Sinking of microplastics (MPs) after biofouling is considered an important mechanisms responsible for the downward transport/sedimentation of MPs in the ocean and freshwaters. Previous studies demonstrated MP sinking caused by an increase in the composite density of MPs after biofouling, while MPs with smaller size or shapes with higher surface area to volume ratios (SA:V), such as films, are speculated to sink faster. In this study, we designed an in situ microcosm to simulate the ambient environmental conditions experienced by floating MPs to elucidate the biofouling and sinking of polyethylene (PE), polypropylene (PP), and expanded-polystyrene (EPS) MPs of various sizes and shapes. Our results showed smaller PE and PP MP granules sank faster than large ones. Even EPS granules of 100 µm diameter, having a much lower density (0.02 mg/mm3) than water, started to sink after 2 weeks of biofouling. Moreover, PE film and fiber MPs with higher SA:V did not sink faster than PE MP granules of the same mass, implying that mechanisms other than SA:V, such as fouling contact area and drag coefficient, play a role in the regulation of biofouling and sinking of MPs.
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Microplásticos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Plásticos , Polietileno , Polímeros , Polipropilenos , Contaminantes Químicos del Agua/análisisRESUMEN
Currently, the industrial application of bioelectrochemical systems (BESs) that are incubated with natural electrochemically active microbes (EABs) is limited due to inefficient extracellular electron transfer (EET) by natural EABs. Notably, recent studies have identified several novel living biomaterials comprising highly efficient electron transfer systems allowing unparalleled proficiency of energy conversion. Introduction of these biomaterials into BESs could fundamentally increase their utilization for a wide range of applications. This review provides a comprehensive assessment of recent advancements in the design of living biomaterials that can be exploited to enhance bioelectrocatalytic performance. Further, modular configurations of abiotic and biotic components promise a powerful enhancement through integration of nano-based artificial mediators and synthetic biology. Herein, recent advancements in BESs are synthesized and assessed, including heterojunctions between conductive nanomaterials and EABs, in-situ hybrid self-assembly of EABs and nano-sized semiconductors, cytoprotection in biohybrids, synthetic biological modifications of EABs and electroactive biofilms. Since living biomaterials comprise a broad range of disciplines, such as molecular biology, electrochemistry and material sciences, full integration of technological advances applied in an interdisciplinary framework will greatly enhance/advance the utility and novelty of BESs. Overall, emerging fundamental knowledge concerning living biomaterials provides a powerful opportunity to markedly boost EET efficiency and facilitate the industrial application of BESs to meet global sustainability challenges/goals.
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Fuentes de Energía Bioeléctrica , Materiales Biocompatibles , Biopelículas , Electrodos , Transporte de Electrón , Biología SintéticaRESUMEN
Human-health risks from microplastics have attracted considerable attention, but little is known about human-exposure pathways and intensities. Recent studies posited that inhalation of atmospheric microplastics was the dominant human-exposure pathway. Herein, our study identified that atmospheric microplastics ingested from deposition during routine dining/drinking activities represent another important exposure pathway. We measured abundances of atmospheric-deposited microplastics of up to 105 items m-2 d-1 in dining/drinking venues, with 90% smaller than 100 µm and a dominance of amorphous fragments rather than fibers. Typical work-life scenarios projected an annual ingestion of 1.9 × 105 to 1.3 × 106 microplastics through atmospheric deposition on diet, with higher exposure rates for indoor versus outdoor dining/drinking settings. Ingestion of atmospheric-deposited microplastics through diet was similar in magnitude to presumed inhalation exposure, but 2-3 orders of magnitude greater than direct ingestion from food sources. Simple mitigation strategies (e.g., covering and rinsing dishware) can substantially reduce the exposure of atmospheric deposition microplastics through diet.
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Microplásticos , Contaminantes Químicos del Agua , Ingestión de Alimentos , Monitoreo del Ambiente , Humanos , Plásticos/toxicidad , Contaminantes Químicos del Agua/análisisRESUMEN
Microplastics are a global concern for their threat to marine ecosystems. Recent studies report a lack of smaller microplastics (<300⯵m) in oceans attributed to a "loss in ocean". Several hypotheses have been proposed to explain the absence of smaller microplastics, but their fate and transport remain an enigma. Our study recovered high concentrations of microplastics (32947⯱â¯15342 items kg-1 dry sediment) from sediments of a coastal plain river network in eastern China, with the <300⯵m fraction accounting for â¼85% of total microplastic particles. Microplastic concentrations were generally higher in sediments from tributary streams and streams surrounded by industrial land use. The high variability of microplastics within the watershed indicates that the distribution of microplastics is regulated by several factors, such as distance to source(s), river flow characteristics, buoyancy behavior, degradation, etc. Fragment and foam forms dominated the small microplastics, while fibers were less prevalent in the <300⯵m fraction and more abundant in downstream sites. The dominance of small microplastics in riverine sediments in this study provides a possible mechanism to explain the relative absence of small microplastics in the ocean, and advocates for quantification of the whole size spectrum of microplastics in future studies of riverine microplastic fluxes.
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Sedimentos Geológicos/análisis , Plásticos/análisis , Ríos , Contaminantes Químicos del Agua/análisis , China , Ciudades , Monitoreo del AmbienteRESUMEN
Recently, there has been a growing research interest on renewable composite due to sustainability concerns. This work demonstrated the possibility of using eucalyptus lignosulfonate calcium (HLS) particles as reinforcement in polyvinyl alcohol (PVA) matrix. 41% and 384.7% improvement of pure PVA tensile strength and Young's modulus were achieved with incorporation of 5 wt% HLS. The above results were ascribed to specific intermolecular interactions between HLS and PVA, suggested by the increasing PVA glass transition and crystalline relaxations temperature, depression of melting point with HLS incorporation. Moreover, this interaction was quantitatively determined by q value of -62.4±10.0 in Kwei equation. Additionally, the remarkable red shift of wavenumber corresponding to hydroxyl group also indicated the formation of strong hydrogen bond in HLS/PVA blend. SEM characterization confirmed that HLS/PVA blends are at least miscible.
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Lignina/análogos & derivados , Fenómenos Mecánicos , Alcohol Polivinílico/química , Enlace de Hidrógeno , Lignina/química , TemperaturaRESUMEN
Surface modification and material improvement is now an important way to improve the osseointegration between bone and uncemented prothesis. The purpose of this study was to investigate the bone ingrowth potential of porous hydroxyapatite (HA) coatings prepared by micro-arc oxidation (MAO) on Ti-3Zr-2Sn-3Mo-25Nb, a new titanium alloy. HA-coated specimens were implanted in the left proximal femoral medullary canal of beagles for 4, 12, and 24 weeks, and uncoated specimens were implanted in the right as a control. The surface morphology and phase composition were investigated with environmental scanning electron microscopy and X-ray diffractometry. The bone ingrowth was assessed by histomorphometry. A pull-out test was performed to assess the mechanical performance of the bone-implant interface. A porous coating was well prepared on the new titanium alloy by using the MAO method. The bone-to-implant contact was significantly higher for the HA-coated group compared to that in the uncoated group. Mechanical tests showed that the HA-coated group had significantly higher maximum force at the bone-implant interface compared to the uncoated specimens. MAO is a suitable coating approach for this new titanium alloy. The HA coating prepared by this approach can significantly promote bone ingrowth and the mechanical performance of the bone-implant interface.
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Aleaciones , Artroplastia de Reemplazo de Cadera/instrumentación , Materiales Biocompatibles Revestidos/química , Durapatita/química , Oseointegración/efectos de los fármacos , Titanio , Animales , Modelos Animales de Enfermedad , Perros , Femenino , Masculino , Microscopía Electrónica de Rastreo , Porosidad , Prótesis e Implantes , Propiedades de SuperficieRESUMEN
The influence of lignin species on the grafting mechanism of lignosulfonate (from eucalyptus and pine, recorded as HLS and SLS, respectively) with acrylic acid (AA) was investigated. The graft polymers were confirmed by the absorption of carbonyl groups in the FTIR spectra. The decreasing phenolic group's content (Ph-OH) is not only due to its participation as grafting site but also to the negative effect of initiator. In the initial period (0-60 min), HLS and SLS both accelerate the polymerization of AA. Additionally, Ph-OH group's content is proportional to product yield (Y%), monomer conversion (C%) and grafting efficiency (GE%), strongly indicating that it acts as active center. Nevertheless, compared with HLS, Y% and C% in SLS grafting system are lower though it has higher Ph-OH group's content, which is due to the quinonoid structure formed by the self-conjugated of phenoxy radical in Guaiacyl unit. Finally, the lignosulfonate grafting mechanism was proposed.