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Delivering biological effector molecules in cultured cells is of fundamental importance to any study or application in which the modulation of gene expression is required. Examples range from generating engineered cell lines for studying gene function to the engineering of cells for cell-based therapies such as CAR-T cells and gene-corrected stem cells for regenerative medicine. It remains a great challenge, however, to deliver biological effector molecules across the cell membrane with minimal adverse effects on cell viability and functionality. While viral vectors have been frequently used to introduce foreign nucleic acids into cells, their use is associated with safety concerns such as immunogenicity, high manufacturing cost, and limited cargo capacity.For photoporation, depending on the laser energy, membrane permeabilization happens either by local heating or by laser-induced water vapor nanobubbles (VNB). In our first study on this topic, we demonstrated that the physical force exerted by suddenly formed VNB leads to more efficient intracellular delivery as compared to mere heating. Next, we explored the use of different photothermal nanomaterials, finding that graphene quantum dots display enhanced thermal stability compared to the more traditionally used gold nanoparticles, hence providing the possibility to increase the delivery efficiency by repeated laser activation. To enable its use for the production of engineered therapeutic cells, it would be better if contact with cells with nondegradable nanoparticles is avoided as it poses toxicity and regulatory concerns. Therefore, we recently demonstrated that photoporation can be performed with biodegradable polydopamine nanoparticles as well. Alternatively, we demonstrated that nanoparticle contact can be avoided by embedding the photothermal nanoparticles in a substrate made from biocompatible electrospun nanofibers. With this variety of photoporation approaches, over the years we demonstrated the successful delivery of a broad variety of biologics (mRNA, siRNA, Cas9 ribonucleoproteins, nanobodies, etc.) in many different cell types, including hard-to-transfect cells such as T cells, embryonic stem cells, neurons, and macrophages.In this Account, we will first start with a brief introduction of the general concept and a historical development of photoporation. In the next two sections, we will extensively discuss the various types of photothermal nanomaterials which have been used for photoporation. We discriminate two types of photothermal nanomaterials: single nanostructures and composite nanostructures. The first one includes examples such as gold nanoparticles, graphene quantum dots, and polydopamine nanoparticles. The second type includes polymeric films and nanofibers containing photothermal nanoparticles as well as composite nanoscale biolistic nanostructures. A thorough discussion will be given for each type of photothermal nanomaterial, from its synthesis and characterization to its application in photoporation, with its advantages and disadvantages. In the final section, we will provide an overall discussion and elaborate on future perspectives.
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Grafito , Nanopartículas del Metal , Nanoestructuras , Puntos Cuánticos , Nanopartículas del Metal/química , Oro/química , Grafito/químicaRESUMEN
Membrane separation is of great significance due to its unique performance in treating wastewater. However, the simultaneous treatment of oily emulsions and other complex pollutants in water remains challenging. Herein, we have proposed a simple strategy to prepare a multifunctional titanium dioxide/silver nanoparticles/polyacrylonitrile (TiO2/AgNPs/PAN) nanofibrous membrane. The experimental results showed that the combination of the hierarchical structure composed of PAN nanofibers and Ag/TiO2 nanoprotrusions contributed to the superhydrophilicity and superoleophobicity (UOCA = 153.3 ± 2.0°). Further, the nanofibrous membrane exhibited a rapid gravity-driven permeate flux (>1829.37 ± 83.51 L m-2 h-1) and an ultrahigh separation efficiency (>99.9%) for the surfactant-stabilized oil/water emulsions. Moreover, due to the synergistic effect between the PAN fibers and TiO2/Ag heterojunction, Rhodamine B dye in water can be removed quickly and efficiently (up to 97.67% in 90 min). More importantly, the obtained nanofibrous membrane exhibited ultrahigh stability in different harsh environments. The design of superoleophobic nanofiber membrane with a high separation efficiency and high photocatalytic activity has great potential for practical applications in the purification of oily wastewater.
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Nanopartículas del Metal , Nanofibras , Nanofibras/química , Colorantes , Emulsiones , Aguas Residuales , Plata , Aceites/química , BacteriasRESUMEN
Inspired by the structure of eukaryotic cells, multicompartmental microcapsules have gained increasing attention. However, challenges remain in the fabrication of "all-aqueous" (i.e., oil-free) microcapsules composed of accurately adjustable hierarchical compartments. This study reports on multicompartmental microcapsules with an innovative architecture. While multicompartmental cores of the microcapsules were fabricated through gas shearing, a shell was applied on the cores through surface gelation of alginate. Different from traditional multicompartmental microcapsules, thus obtained microcapsules have well-segregated compartments while the universal nature of the surface-gelation method allows us to finely tune the shell thicknesses of the microcapsules. The microcapsules are highly stable and cytocompatible and allow repeated enzymatic cascade reactions, which might make them of interest for complex biocatalysis or for mimicking physiological processes.
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Alginatos , Agua , Alginatos/química , Cápsulas/química , Emulsiones/químicaRESUMEN
Herein, a high-performance fluorescence probe, namely H4, based on intramolecular charge transfer (ICT) mechanism was developed. H4 could serve as fluorescent probe for detection acidic pH change in environment with outstanding sensitivity, short response time (<10 s), low hemolysis effect (<0.3%) and excellent photostability (>120 min). H4 exhibits a good linear relationship (R2 = 0.9901, Y = 22.0409X-58.3397) characteristics in range of pH 2.2-7.4 with pKa 4.3. In addition, the probe can be also made as fluorescent test sheets and further used as a portable sensor to enhance the screening speed to achieve detection of H+ in real-time. Further, H4 determined H+ in real food samples (milk, shrimps, and scallops) has excellent recoveries (98-105%), which making it of great potential use in food freshness evaluation. Initially, its favorable behavior for detecting H+ change is successfully illustrated in living onion tissues and zebrafish, which allows qualitative visualization of acid pH changes in in biological systems.
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Colorimetría , Colorantes Fluorescentes , Animales , Colorantes Fluorescentes/química , Concentración de Iones de Hidrógeno , Indoles , Pez CebraRESUMEN
Stimuli-responsive nanobubbles have received increased attention for their application in spatial and temporal resolution of diagnostic techniques and therapies, particularly in multiple imaging methods, and they thus have significant potential for applications in the field of biomedicine. This review presents an overview of the recent advances in the development of stimuli-responsive nanobubbles and their novel applications. Properties of both internal- and external-stimuli responsive nanobubbles are highlighted and discussed considering the potential features required for biomedical applications. Furthermore, the methods used for synthesis and characterization of nanobubbles are outlined. Finally, novel biomedical applications are proposed alongside the advantages and shortcomings inherent to stimuli-responsive nanobubbles.
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Investigación Biomédica , Nanoestructuras/química , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Fluorescence probe combines with fluorescence imaging technology has become the most powerful analytical method with their great advantages of high sensitivity and selectivity and real-time monitoring. Ni2+ is widely distributed in food, environment and living animals, thereof, it is of great significance for detection Ni2+ with high selectivity. Herein, a simple strategy is proposed to design and synthesiz a small molecule fluorescent probe Y1 by using "one-pot" method. The spectroscopic behaviors including UV-Vis absorption and fluorescence emission spectrum have been used to verify the feasibility of probe towards Ni2+ in water/EtOH (v/v = 2:8) mixtures under neutral condition. As expected, Y1 offers high selectivity and sensitivity for detection Ni2+ in aqueous solution with a good linear relationship and low detection limit within Ni2+ concentration variation from 0 to 13 µM (DOL = 0.0038 µM, R2 = 0.9983). It is remarkable that Y1 can be applied for real-time visualization Ni2+ change in sprouted potato and zebrafish with great photo-stability, highlighting that the practicability and feasibility of Y1 to detect and monitor Ni2+ in the field of food industry and biomedical field.
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Colorimetría , Colorantes Fluorescentes/química , Níquel/análisis , Solanum tuberosum/química , Animales , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Rayos Ultravioleta , Pez CebraRESUMEN
Extrinsic probes have outstanding properties for intracellular labeling to visualize dynamic processes in and of living cells, both in vitro and in vivo. Since extrinsic probes are in many cases cell-impermeable, different biochemical, and physical approaches have been used to break the cell membrane barrier for direct delivery into the cytoplasm. In this Review, these intracellular delivery strategies are discussed, briefly explaining the mechanisms and how they are used for live-cell labeling applications. Methods that are discussed include three biochemical agents that are used for this purpose-purpose-different nanocarriers, cell penetrating peptides and the pore-foraming bacterial toxin streptolysin O. Most successful intracellular label delivery methods are, however, based on physical principles to permeabilize the membrane and include electroporation, laser-induced photoporation, micro- and nanoinjection, nanoneedles or nanostraws, microfluidics, and nanomachines. The strengths and weaknesses of each strategy are discussed with a systematic comparison provided. Finally, the extrinsic probes that are reported for intracellular labeling so-far are summarized, together with the delivery strategies that are used and their performance. This combined information should provide for a useful guide for choosing the most suitable delivery method for the desired probes.
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Péptidos de Penetración Celular , Membrana Celular , Citoplasma , Rayos LáserRESUMEN
Barcodes have attracted widespread attention, especially for the multiplexed bioassays and anti-counterfeiting used toward medical and biomedical applications. An enabling gas-shearing approach is presented for generating 10-faced microspherical barcodes with precise control over the properties of each compartment. As such, the color of each compartment could be programmatically adjusted in the 10-faced memomicrospheres by using pregel solutions containing different combinations of fluorescent nanoparticles. During the process, three primary colors (red, green, and blue) are adopted to obtain up to seven merged fluorescent colors for constituting a large amount of coding as well as a magnetic compartment, capable of effective and robust high-throughput information-storage. More importantly, by using the biocompatible sodium alginate to construct the multicolor microspherical barcodes, the proposed technology is likely to advance the fields of food and pharmaceutics anti-counterfeiting. These remarkable properties point to the potential value of gas-shearing in engineering microspherical barcodes for biomedical applications in the future.
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Nanopartículas , Bioensayo , ColorantesRESUMEN
Nanoparticle mediated laser-induced photoporation is a physical cell membrane disruption approach to directly deliver extrinsic molecules into living cells, which is particularly promising in applications for both adherent and suspension cells. In this work, we explored surface modifications of graphene quantum dots (GQD) and reduced graphene oxide (rGO) with polyethylene glycol (PEG) and polyethyleneimine (PEI) to enhance colloidal stability while retaining photoporation functionality. After photoporation with FITC-dextran 10 kDa (FD10), the percentage of positive HeLa cells (81% for GQD-PEG, 74% for rGO-PEG and 90% for rGO-PEI) increased approximately two-fold compared to the bare nanomaterials. While for Jurkat suspension cells, the photoporation efficiency with polymer-modified graphene-based nanomaterial reached as high as 80%. Cell viability was >80% in all these cases. In addition, polymer functionalization proved to be beneficial for the delivery of larger macromolecules (FD70 and FD500) as well. Finally, we show that rGO is suitable for photoporation using a near-infrared laser to reach 80% FD10 positive HeLa cells at 80% cell viability. We conclude that modification of graphene-based nanoparticles with PEG and especially PEI provide better colloidal stability in cell medium, resulting in more uniform transfection and overall increased efficiency.
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Grafito/química , Polietilenglicoles/farmacología , Polietileneimina/farmacología , Puntos Cuánticos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Técnicas de Transferencia de Gen , Células HeLa , Humanos , Células Jurkat , Rayos Láser , Nanoestructuras/química , Transfección/métodos , Transfección/estadística & datos numéricosRESUMEN
Long-term in vivo imaging of cells is crucial for the understanding of cellular fate in biological processes in cancer research, immunology, or in cell-based therapies such as beta cell transplantation in type I diabetes or stem cell therapy. Traditionally, cell labeling with the desired contrast agent occurs ex vivo via spontaneous endocytosis, which is a variable and slow process that requires optimization for each particular label-cell type combination. Following endocytic uptake, the contrast agents mostly remain entrapped in the endolysosomal compartment, which leads to signal instability, cytotoxicity, and asymmetric inheritance of the labels upon cell division. Here, we demonstrate that these disadvantages can be circumvented by delivering contrast agents directly into the cytoplasm via vapor nanobubble photoporation. Compared to classic endocytic uptake, photoporation resulted in 50 and 3 times higher loading of fluorescent dextrans and quantum dots, respectively, with improved signal stability and reduced cytotoxicity. Most interestingly, cytosolic delivery by photoporation prevented asymmetric inheritance of labels by daughter cells over subsequent cell generations. Instead, unequal inheritance of endocytosed labels resulted in a dramatic increase in polydispersity of the amount of labels per cell with each cell division, hindering accurate quantification of cell numbers in vivo over time. The combined benefits of cell labeling by photoporation resulted in a marked improvement in long-term cell visibility in vivo where an insulin producing cell line (INS-1E cell line) labeled with fluorescent dextrans could be tracked for up to two months in Swiss nude mice compared to 2 weeks for cells labeled by endocytosis.
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The pollution of heavy metals such as Cu2+ is still serious and the discharge of sewage of Cu2+ will cause damage to soil environment and human health. Herein, a biomass-based solid-state fluorescence detection platform (CPU-CDs) was developed as fluorescent sensor for detection Cu2+ via fluorescence and colorimetric dual-model methods in real time. CPU-CDs was composed of xylan-derived CDs (U-CDs) and cotton cellulose paper, which exhibiting good reusability, non-toxicity, excellent fluorescence characteristics and high biocompatibility. Further, CPU-CDs displayed high effectiveness and sensitivity for Cu2+ with the detection limit as low as 0.14 µM, which was well below U.S. EPA safety levels (20 µM). Practical application indicated that CPU-CDs could achieve precision response of Cu2+ change in real environment water samples with good recovery range of 90 %-119 %. This strategy demonstrated a promising biomass solid-state fluorescence sensor for Cu2+ detection for water treatment research, which is of great significance in dealing with water pollution caused by heavy metal ions.
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Puntos Cuánticos , Humanos , Espectrometría de Fluorescencia/métodos , Límite de Detección , Xilanos , Celulosa , Carbono , Colorantes FluorescentesRESUMEN
Recently, the demand for healthcare products especially wearable smart masks is increasing. The biosafety and degradability of smart masks are crucial for human health and environmental protection. However, the development of biodegradable and biocompatible fibrous membranes with high filtration efficiency and low pressure drop is still a challenge. How to realize the collaborative improvement between air filtration efficiency and pressure drop of the nanofibrous membrane is still a challenge. Here, a tribo-charge enhanced and biodegradable nanofibrous membranes (TCB NFMs) with highly fluffy structure for air filtration and self-powered respiration monitoring systems is reported for the first time. The filtration efficiency and pressure drop of the prepared membranes for 0.3 µm NaCl particulates is 99.971% and 41.67 Pa. The TCB NFMs based smart mask possesses a series of satisfactory and excellent characteristics, such as self-powered, biodegradable, biocompatible, high filtration efficiency, and low pressure drop, which is highly promising for application in air filtration systems and intelligent wearable respiration monitoring systems.
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Filtros de Aire , Nanofibras , Humanos , Celulosa , Conservación de los Recursos Naturales , RespiraciónRESUMEN
Water and soil pollution caused by Cu2+ is not conducive to sustainable development of environment and could cause damage to environment and even human body. Currently, fluorescent sensor solutions analysis method has been used for Cu2+ detection, but they also suffer from drawbacks including easy leakage, difficult storage, and inaccurate. Herein, a green solid-state biomass fluorescence platform (NBU-CDs) consisting of xylan-derived carbon dots (U-CDs) and polylactic acid/polycaprolactone (PLA/PCL) was designed by using in situ electrospinning technology. The prepared NBU-CDs fluorescence platform showed good fluorescence effect and can be served as fluorescence sensor for detecting Cu2+ with high sensitively, selectively and low detection limit (LOD = 0.83 µM). The practical applications of NBU-CDs exhibited high specificity for Cu2+ detection in zebrafish, water samples (school lake, Xuanwu Lake and Yangtze River) with high recovery rates of 97 %-104 % and soil (pond soil, grassland soil and bamboo soil) samples, respectively. The developed fluorescence platform was utilized to predict water and soil safety by monitoring Cu2+ concentration and provides a new strategy for Cu2+ detection.
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Nanofibras , Puntos Cuánticos , Humanos , Animales , Xilanos , Carbono , Biomasa , Pez Cebra , Cobre/análisis , Agua/análisis , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes , SueloRESUMEN
In order to reduce the dependence on fossil energy products, natural fiber/polymer hybrid composites have been increasingly researched. The high price of the quartz optical fibers and glass optical fibers has greatly inspired researchers to engage in the research on polymer optical fibers. Herein, transparent fibers based on plant fibers were innovatively prepared for the first time by delignification and impregnating epoxy diluted with acetone. The epoxy improved the thermal stability of the fiber without deteriorating its mechanical properties, and also endowed the fiber with the property of transparency. The tensile strength of transparent fibers of three diameters were 34.5, 58.6 and 100.3 MPa, respectively and the corresponding Young's modulus reached 1.1, 1.7 and 2.3 GPa, respectively. In addition, the light-conducting properties of transparent fibers were displayed with a green laser and the fibers displayed good light transmission along the fiber growth direction. Transparent fibers are expected to be used in optical fibers because of their high thermal stability, good mechanical properties and light-conducting properties.
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Fibras Ópticas , Polímeros , Resistencia a la TracciónRESUMEN
Picric acid (PA) is highly water-soluble, the fact makes it stand out as the most hazardous environment pollutant. Therefore, accurate determination of PA is of great significance for human health and environmental protection. Herein, a novel indole-based fluorescent sensor (H1) with good water solubility and fluorescence stability was reported. H1 exhibited 'turn-off' fluorescence response for PA with fast reaction rate (<30 s), unique specificity and excellent selectivity and high sensitivity (limit of detection = 34 nM). Further, H1 was successfully applied to detect PA in real samples (tap water, Yangtze River, Xuanwu Lake, soil, food, fish and shrimp) with satisfactory recoveries at three spiking levels ranging from 98.0 to 112.0 %. In addition, H1 displayed high biocompatibility in mung beans and fresh blood. Moreover, aiming to attain portable analysis, H1 was composited with biomass cellulose paper (H1-FP) and integrated with smartphone for construction as a solid-state fluorescence platform to achieve fast and visual detection of PA in suit with significant stability, high sensitively and selectivity. The establishment of this sensing approach is expected to offer new insight into rapid, selective, and sensitive detection of major pollutants for food and environmental safety.
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Celulosa , Contaminantes Ambientales , Humanos , Biomasa , Espectrometría de Fluorescencia , Agua , Colorantes FluorescentesRESUMEN
Bacterial infections pose a serious threat to public health, causing worldwide morbidity and about 80 % of bacterial infections are related to biofilm. Removing biofilm without antibiotics remains an interdisciplinary challenge. To solve this problem, we presented a dual-power driven antibiofilm system Prussian blue composite microswimmers based on alginate-chitosan, which designed into an asymmetric structure to achieve self-driven in the fuel solution and magnetic field. Prussian blue embedded in the microswimmers given it the ability to convert light and heat, catalyze Fenton reaction, and produce bubbles and reactive oxygen species. Moreover, with the addition of Fe3O4, the microswimmers could move in group under external magnetic field. The composite microswimmers displayed excellent antibacterial activity against S. aureus biofilm with an efficiency as high as 86.94 %. It is worth mentioning that the microswimmers were fabricated with device-simple and low-cost gas-shearing method. This system integrating physical destruction, chemical damage such chemodynamic therapy and photothermal therapy, and finally kill the plankton bacteria embedded in biofilm. This approach may cause an autonomous, multifunctional antibiofilm platform to promote the present most areas with harmful biofilm difficult to locate the surface for removal.
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Quitosano , Quitosano/farmacología , Quitosano/química , Alginatos , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , BiopelículasRESUMEN
Adhesive hydrogels containing quaternary ammonium salt (QAS) moieties have shown attractive advantages in treatment for acute wounds, attributed to their high performances in wound sealing and sterilization. However, the introduction of QAS commonly leads to high cytotoxicity and adhesive deterioration. Herein, aimed to solve these two issues, a self-adaptive dressing with delicate spatiotemporal responsiveness is developed by employing cellulose sulfate (CS) as dynamic layers to coat QAS-based hydrogel. In detail, due to the acid environment of wound in the early stages of healing, the CS coating will quickly detach to expose the active QAS groups for maximum disinfectant efficacy; meanwhile, as the wound gradually heals and recovers to a neutral pH, the CS will remain stable to keep QAS screened, realizing a high cell growth-promoting activity for epithelium regeneration. Additionally, attributed to the synergy of temporary hydrophobicity by CS and slow water absorption kinetics of the hydrogel, the resultant dressing possesses outstanding wound sealing and hemostasis performance. At last, this work anticipates this approach to intelligent wound dressings based on dynamic and responsive intermolecular interaction can also be applied to a wide range of self-adaptive biomedical materials employing different chemistries for applications in medical therapy and health monitoring.
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Hidrogeles , Cicatrización de Heridas , Hidrogeles/farmacología , Hidrogeles/química , Antibacterianos/farmacología , Antibacterianos/química , Vendajes , Materiales Biocompatibles , AdhesivosRESUMEN
In recent decades, three-dimensional (3D) cell culture technologies have been developed rapidly in the field of tissue engineering and regeneration, and have shown unique advantages and great prospects in the differentiation of stem cells. Herein, the article reviews the progress and advantages of 3D cell culture technologies in the field of stem cell differentiation. Firstly, 3D cell culture technologies are divided into two main categories: scaffoldless and scaffolds. Secondly, the effects of hydrogels scaffolds and porous scaffolds on stem cell differentiation in the scaffold category were mainly reviewed. Among them, hydrogels scaffolds are divided into natural hydrogels and synthetic hydrogels. Natural materials include polysaccharides, proteins, and their derivatives, focusing on hyaluronic acid, collagen and polypeptides. Synthetic materials mainly include polyethylene glycol (PEG), polyacrylic acid (PAA), polyvinyl alcohol (PVA), etc. In addition, since the preparation techniques have a large impact on the properties of porous scaffolds, several techniques for preparing porous scaffolds based on different macromolecular materials are reviewed. Finally, the future prospects and challenges of 3D cell culture in the field of stem cell differentiation are reviewed. This review will provide a useful guideline for the selection of materials and techniques for 3D cell culture in stem cell differentiation.
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Materiales Biocompatibles , Andamios del Tejido , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Andamios del Tejido/química , Ácido Hialurónico/farmacología , Ingeniería de Tejidos/métodos , Diferenciación Celular , Colágeno/farmacología , Hidrogeles/farmacología , Hidrogeles/química , Técnicas de Cultivo Tridimensional de Células , Péptidos/farmacologíaRESUMEN
The emergence, spread and difficult removal of bacteria biofilm, represent an ever-increasing persistent infections and medical complications challenge worldwide. Herein, a self-propelled system Prussian blue micromotor (PB MMs) were constructed by gas-shearing technology for efficient degradation of biofilms by combining chemodynamic therapy (CDT) and photothermal therapy (PTT). With the interpenetrating network crosslinked by alginate, chitosan (CS) and metal ions as the substrate, PB was generated and embedded in the micromotor at the same time of crosslinking. The micromotors are more stable and could capture bacteria with the addition of CS. The micromotors show excellent performance, containing photothermal conversion, reactive oxygen species (ROS) generation and bubble produced by catalyzing Fenton reaction for motion, which served as therapeutic agent could chemically kill bacteria and physically destroy biofilm. This research work opens a new path of an innovative strategy to efficiently remove biofilm.
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Quitosano , Alginatos , Biopelículas , FerrocianurosRESUMEN
Recently, polymers capable of repeatedly self-healing physical damage and restoring mechanical properties have attracted extensive attention. Among the various supramolecular chemistry, hydrogen-bonding (H-bonding) featuring reversibility, directionality and high per-volume concentration has become one of the most attractive directions for the development of self-healing polymers (SHPs). Herein, we review the recent advances in the design of high-performance SHPs based on different H-bonding types, for example, H-bonding motifs and excessive H-bonding. In particular, the effects of the structural design of SHPs on their mechanical performance and healing efficiency are discussed in detail. Moreover, we also summarize how to employ H-bonding-based SHPs for the preparation of self-healable electronic devices, focusing on promising topics, including energy harvesting devices, energy storage devices, and flexible sensing devices. Finally, the current challenges and possible strategies for the development of H-bonding-based SHPs and their smart electronic applications are highlighted.