RESUMEN
Many biological species combine the helical organization of cellulose or chitin microfibrils with broadband light absorption of black melanin to produce brilliant structural colors with metallic and glossy effects and other diverse functions. In this work, based on core-shell CNC@PDA chiral nanorods consisting of cellulose nanocrystals (CNCs) as the core and melanin-like polydopamine (PDA) as the shell that can form well-defined chiral liquid crystal phases, we report chiral photonic materials that closely mimic the unique coloration mechanisms and functionalities mastered by several biological species. The photonic films formed by such single CNC@PDA nanorods have brilliant iridescent structural colors originating from selective reflection of circularly polarized lights by the helical organization of CNC@PDAs across the films. Furthermore, the colors of such films have background-independent brightness, high visibility, and metallic effects that arise from the light absorption of the PDA component. Especially, the color ranges and metallic effects of the films can be conveniently tuned by varying the thickness of the PDA shell. In addition, the UV absorption and hygroscopic properties of PDA endow these CNC@PDA films with efficient broadband UV shielding and sensitive humidity-induced dynamic color changes. Due to the mussel-like superior adhesion of PDA, CNC@PDA-based photonic coatings can be formed conformably onto diverse kinds of substrates. A shiny eye shadow with viewing angle-dependent colorful patterns was used to demonstrate the potential applications. With combinations of multiple unique properties in one photonic material fabricated from a single building block, these CNC@PDA-based films are expected to have potential applications in cosmetics, UV protection, anticounterfeiting, chiral reflectors, etc.
Asunto(s)
Cosméticos , Nanotubos , Biomimética , Celulosa/química , Humedad , Melaninas/químicaRESUMEN
Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-ß1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1ß and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds.
Asunto(s)
Alginatos/farmacología , Colágeno/farmacología , Hidrogeles/farmacología , Células Madre Mesenquimatosas/citología , Piel/efectos de los fármacos , Cordón Umbilical/citología , Cicatrización de Heridas , Animales , Materiales Biocompatibles/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Inflamación/patología , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The current work investigates how the nanoscale conformal coating layers of non-chiral polymeric materials can influence the chiral nematic liquid crystal (CLC) behaviors of the rodlike cellulose nanocrystals (CNCs), the bio-derived nanomaterials that have attracted significant attention. For this, we developed strategies to coat the CNC rods on the single-particle level with a homogeneous bioinspired polydopamine (PDA) layer, leading to well-defined core-shell CNC@PDA rods with various PDA coating thicknesses and excellent colloidal stability. Comprehensive investigation revealed that the CNC@PDA hybrid nanorods in concentrated suspensions form well-defined nematic liquid crystal phases with clear phase separation behavior that depend on the rod concentrations and ionic strengths, typical of charged rods. Most intriguingly, the nematic LC phases formed by the CNC@PDA rods with the PDA coating thickness achieved herein are indeed the perfect CLC phases, which form following the classic pathway of nucleation and coalesce of chiral tactoids and have colorful chiral fingerprints standing out from the dark suspensions. The pitches of the CLC phase increase sharply with increasing PDA coating thicknesses and are significantly larger than those of the pristine CNCs. Such observations can be attributed to the blurring effects of the PDA coating on the intrinsic surface chiral features of CNC of whatever origins that drive the formation of the CLC phases, resulting in weakening chiral interactions between CNC@PDA rods. Besides benefiting the understanding of the long-sought origin of the CLC phases of the pristine CNC, the current work demonstrates the possibility of controlling the CLC phase behaviors of CNC by tuning the thickness of the coating materials and also serves as the first example of directly transferring the unique chirality of CNC to other non-chiral materials.
Asunto(s)
Cristales Líquidos , Nanopartículas , Nanoestructuras , Celulosa , SuspensionesRESUMEN
With expanding applications of hydrogels in diverse fields ranging from biomaterials to sensors, actuators, and soft robotics, there is an urgent need to endow one single gel with multiple physicochemical properties, such as stimuli-responsiveness, injectability, self-healing, and tunable internal structures. However, it is challenging to simultaneously incorporate these highly sought-after properties into one single gel. Herein, a conceptual hydrogel system with all of these properties is presented via combining bioconjugate chemistry, filamentous viruses, and dynamic covalent bonds. Nanofilamentous bioconjugates with diol affinity were prepared by coupling a tailor-synthesized low-p Ka phenylboronic acid (PBA) derivative to a well-defined green nanofiber the M13 virus with a high aspect ratio (PBA-M13). Dynamic hydrogels with tunable mechanical strength were prepared by using multiple diol-containing agents such as poly(vinyl alcohol) to cross-link such PBA-M13 via the classic boronic-diol dynamic bonds. The as-prepared hydrogels exhibit excellent injectability and self-healing behaviors as well as easy chemical accessibility of the PBA moieties on the virus backbone inside the gel matrix. Ordered internal structures were imparted into virus-based hydrogels by simple shear-induced alignment of the virus nanofibers. Furthermore, unique hydrogels with chiral internal structures were fabricated through in situ gelation induced by diffusion of diol-containing molecules to fix the chiral liquid crystal phase of the PBA-M13 virus. Sugar responsiveness of this gel leads to a glucose-regulated release behavior of payloads such as insulin. All of these properties have been implemented at physiological pH, which will facilitate future applications of these hydrogels as biomaterials.
Asunto(s)
Bacteriófago M13/química , Glucosa/metabolismo , Hidrogeles/química , Nanofibras/química , Ácidos Borónicos/química , Concentración de Iones de Hidrógeno , Inyecciones , Insulina/metabolismo , Cristales Líquidos/química , Modelos Moleculares , Conformación Molecular , Alcohol Polivinílico/químicaRESUMEN
Inadvertent photosensitizer-activation and singlet-oxygen generation hampers clinical application of photodynamic therapies of superficial tumors or subcutaneous infections. Therefore, a reversible photoswitchable system was designed in micellar nanocarriers using ZnTPP as a photosensitizer and BDTE as a photoswitch. Singlet-oxygen generation upon irradiation didnot occur in closed-switch micelles with ZnTPP/BDTE feeding ratios >1:10. Deliberate switch closure/opening within 65-80 min was possible through thin layers of porcine tissue in vitro, increasing for thicker layers. Inadvertent opening of the switch by simulated daylight, took several tens of hours. Creating deliberate cell damage and prevention of inadvertent damage in vitro and in mice could be done at lower ZnTPP/BDTE feeding ratios (1:5) in open-switch micelles and at higher irradiation intensities than inferred from chemical clues to generate singlet-oxygen. The reduction of inadvertent photosensitizer activation in micellar nanocarriers, while maintaining the ability to kill tumor cells and infectious bacteria established here, brings photodynamic therapies closer to clinical application.
Asunto(s)
Nanoestructuras/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Oxígeno Singlete/metabolismo , Células 3T3 , Animales , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Espectroscopía de Resonancia por Spin del Electrón , Femenino , Células HeLa , Humanos , Lactonas/química , Ratones , Ratones Endogámicos BALB C , Micelas , Fármacos Fotosensibilizantes/administración & dosificación , Polietilenglicoles/química , Porfirinas/química , Oxígeno Singlete/química , Espectrofotometría Ultravioleta , Zinc/químicaRESUMEN
Traditionally, containers made from steel or other metals are not good for making tea, probably due to the fact that polyphenol components in tea can chelate with metal ions. A similar reason might stand behind the observations as reported herein. During the coating of well-defined metal-organic framework (MOF) crystalline particles with polydopamine (PDA) via pH-induced self-polymerization of dopamine, we found that MOF templates automatically etch off during the coating, giving rise to nonspherical PDA capsules that inherit the morphologies of the templates. Such self-etching of MOF templates is ascribed to the chelation of the metal nodes of the MOFs by the catechol moieties in the PDA layer. In addition, the self-etching of the zeolitic imidazolate framework-8 (ZIF-8) with a truncated cubic shape probably follows a crystalline facet-dependent fashion, resulting in intermediate yolk-shell structures with ZIF-8 cargos of various shapes inside a highly biocompatible PDA shell. Incubation of such intermediate hybrid particles with the cancerous HeLa cell line leads to pronounced cytotoxicity, which is tentatively connected with the cellular internalization of the ZIF@PDA nanoparticles because of the cell affinity of the PDA layer. Subsequently, the continuous release of Zn2+ by the self-etching of the encapsulated ZIF-8 inside the cell increases intracellular Zn2+ to a harmful level. Therefore, intracellular delivery of metal ions is probably realized, which might offer a novel way for cancer therapy.
Asunto(s)
Estructuras Metalorgánicas/química , Cápsulas , Células HeLa , Humanos , Indoles , Iones , Metales , Nanosferas , PolímerosRESUMEN
Molecular chaperones can elegantly fine-tune its hydrophobic/hydrophilic balance to assist a broad spectrum of nascent polypeptide chains to fold properly. Such precious property is difficult to be achieved by chaperone mimicking materials due to limited control of their surface characteristics that dictate interactions with unfolded protein intermediates. Mixed shell polymeric micelles (MSPMs), which consist of two kinds of dissimilar polymeric chains in the micellar shell, offer a convenient way to fine-tune surface properties of polymeric nanoparticles. In the current work, we have fabricated ca. 30 kinds of MSPMs with finely tunable hydrophilic/hydrophobic surface properties. We investigated the respective roles of thermosensitive and hydrophilic polymeric chains in the thermodenaturation protection of proteins down to the molecular structure. Although the three kinds of thermosensitive polymers investigated herein can form collapsed hydrophobic domains on the micellar surface, we found distinct capability to capture and release unfolded protein intermediates, due to their respective affinity for proteins. Meanwhile, in terms of the hydrophilic polymeric chains in the micellar shell, poly(ethylene glycol) (PEG) excels in assisting unfolded protein intermediates to refold properly via interacting with the refolding intermediates, resulting in enhanced chaperone efficiency. However, another hydrophilic polymer-poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) severely deteriorates the chaperone efficiency of MSPMs, due to its protein-resistant properties. Judicious combination of thermosensitive and hydrophilic chains in the micellar shell lead to MSPM-based artificial chaperones with optimal efficacy.
Asunto(s)
Micelas , Fosforilcolina/análogos & derivados , Ácidos Polimetacrílicos/química , Desnaturalización Proteica , Replegamiento Proteico , Materiales Biomiméticos , Anhidrasa Carbónica I/química , Dicroismo Circular , Dispersión Dinámica de Luz , Glicoles de Etileno/síntesis química , Glicoles de Etileno/química , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Electrónica de Transmisión , Fosforilcolina/síntesis química , Fosforilcolina/química , Poliésteres/síntesis química , Poliésteres/química , Propiedades de Superficie , TemperaturaRESUMEN
The current work reports an intriguing discovery of how the force exerted on protein complexes like filamentous viruses by the strong interchain repulsion of polymer brushes can induce subtle changes of the constituent subunits at the molecular scale. Such changes transform into the macroscopic rearrangement of the chiral ordering of the rodlike virus in three dimensions. For this, a straightforward "grafting-to" PEGylation method has been developed to densely graft a filamentous virus with poly(ethylene glycol) (PEG). The grafting density is so high that PEG is in the polymer brush regime, resulting in straight and thick rodlike particles with a thin viral backbone. Scission of the densely PEGylated viruses into fragments was observed due to the steric repulsion of the PEG brush, as facilitated by adsorption onto a mica surface. The high grafting density of PEG endows the virus with an isotropic-nematic (I-N) liquid crystal (LC) phase transition that is independent of the ionic strength and the densely PEGylated viruses enter into the nematic LC phase at much lower virus concentrations. Most importantly, while the intact virus and the one grafted with PEG of low grafting density can form a chiral nematic LC phase, the densely PEGylated viruses only form a pure nematic LC phase. This can be traced back to the secondary to tertiary structural change of the major coat protein of the virus, driven by the steric repulsion of the PEG brush. Quantitative parameters characterising the conformation of the grafted PEG derived from the grafting density or the I-N LC transition are elegantly consistent with the theoretical prediction.
Asunto(s)
Proteínas de la Cápside/química , Cristales Líquidos/química , Polietilenglicoles/química , Virus/química , Adsorción , Silicatos de Aluminio/química , Proteínas de la Cápside/ultraestructura , Microscopía de Fuerza Atómica , Modelos Moleculares , Transición de Fase , Propiedades de Superficie , Virus/ultraestructuraRESUMEN
In the past decades, polymer based nanoscale polymeric assemblies have attracted continuous interest due to their potential applications in many fields, such as nanomedicine. Many efforts have been dedicated to tailoring the three-dimensional architecture and the placement of functional groups at well-defined positions within the polymeric assemblies, aiming to augment their function. To achieve such goals, in one way, novel polymeric building blocks can be designed by controlled living polymerization methodology and advanced chemical modifications. In contrast, by focusing on the end function, others and we have been practicing strategies of cooperative self-assembly of multiple polymeric building blocks chosen from the vast library of conventional block polymers which are easily available. The advantages of such strategies lie in the simplicity of the preparation process and versatile choice of the constituent polymers in terms of their chemical structure and functionality as well as the fact that cooperative self-assembly based on supramolecular interactions offers elegant and energy-efficient bottom-up strategies. Combination of these principles has been exploited to optimize the architecture of polymeric assemblies with improved function, to impart new functionality into micelles and to realize polymeric nanocomplexes exhibiting functional integration, similar to some natural systems like artificial viruses, molecular chaperones, multiple enzyme systems, and so forth. In this Account, we shall first summarize several straightforward designing principles with which cooperative assembly of multiple polymeric building blocks can be implemented, aiming to construct polymeric nanoassemblies with hierarchal structure and enhanced functionalities. Next, examples will be discussed to demonstrate the possibility to create multifunctional nanoparticles by combination of the designing principles and judiciously choosing of the building blocks. We focus on multifunctional nanoparticles which can partially address challenges widely existing in nanomedicine such as long blood circulation, efficient cellular uptake, and controllable release of payloads. Finally, bioactive polymeric assemblies, which have certain functions closely mimicking those of some natural systems, will be used to conceive the concept of functional integration.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Sustancias Macromoleculares/química , Nanopartículas/química , Polímeros/química , Materiales Biomiméticos , Micelas , Chaperonas Moleculares/química , Permeabilidad , Polímeros/síntesis química , Propiedades de SuperficieRESUMEN
The disruption of Aß homeostasis, which results in the accumulation of neurotoxic amyloids, is the fundamental cause of Alzheimer's disease (AD). Molecular chaperones play a critical role in controlling undesired protein misfolding and maintaining intricate proteostasis inâ vivo. Inspired by a natural molecular chaperone, an artificial chaperone consisting of mixed-shell polymeric micelles (MSPMs) has been devised with tunable surface properties, serving as a suppressor of AD. Taking advantage of biocompatibility, selectivity toward aberrant proteins, and long blood circulation, these MSPM-based chaperones can maintain Aß homeostasis by a combination of inhibiting Aß fibrillation and facilitating Aß aggregate clearance and simultaneously reducing Aß-mediated neurotoxicity. The balance of hydrophilic/hydrophobic moieties on the surface of MSPMs is important for their enhanced therapeutic effect.
Asunto(s)
Péptidos beta-Amiloides/química , Homeostasis , Micelas , Chaperonas Moleculares/química , Polímeros/química , Dicroismo Circular , Cinética , Microscopía Electrónica de Transmisión , Espectrofotometría UltravioletaRESUMEN
We have fabricated a mixed-shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroEL-GroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co-assembly of block copolymers poly(lactide-b-poly(ethylene oxide) (PLA-b-PEG) and poly(lactide)-b-poly(N-isopropylacryamide) (PLA-b-PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core-shell-corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone-like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydraseâ B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more-complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM-based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases.
Asunto(s)
Resinas Acrílicas/química , Lactatos/química , Chaperonas Moleculares/química , Polietilenglicoles/química , Polímeros/química , Proteínas/química , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Soluciones , TemperaturaRESUMEN
Wound healing is a well-orchestrated dynamic and interactive process, which needs a favorable microenvironment and suitable angiogenesis. Platelet derived growth factor-BB (PDGF-BB) plays a crucial role in wound healing. However, the short half-life of PDGF-BB limits its efficacy. In the present study, we successfully synthesized an injectable hydrogel with sodium alginate (SA) and dextran (Dex) as a delivery system to simultaneously deliver PDGF-BB and bone marrow-derived mesenchymal stem cells (BMSCs) in the wound. Our work demonstrates that the PDGF-BB protein enhanced the survival, migration and endothelial cell (EC) differentiation of BMSCs in vitro. The PDGF-BB/SA/Dex hydrogels could sustainably release PDGF-BB with excellent biocompatibility in vitro and in vivo. Besides, these composite hydrogels loaded with BMSCs could accelerate wound healing by improving epithelialization and collagen deposition. In addition, the PDGF-BB/SA/Dex hydrogels promoted the EC-differentiation of transplanted BMSCs and proliferation of hair follicle stem cells in the wound. Furthermore, the expressions of angiogenesis-specific markers, PDGFR-ß, p-PI3K, p-Akt, and p-eNOS, were obviously increased in the PDGF-BB/SA/Dex/BMSCs group. In conclusion, the PDGF-BB/SA/Dex injectable hydrogels could accelerate BMSC-mediated skin wound healing by promoting angiogenesis via the activation of the PDGF-BB/PDGFR-ß-mediated PI3K/Akt/eNOS pathway, which may provide a new therapeutic strategy for stem cell therapy in wound healing.
Asunto(s)
Alginatos/farmacología , Materiales Biocompatibles/farmacología , Dextranos/farmacología , Hidrogeles/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Alginatos/administración & dosificación , Alginatos/química , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Dextranos/administración & dosificación , Dextranos/química , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/química , Ensayo de Materiales , Células Madre Mesenquimatosas/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/administración & dosificación , Factor de Crecimiento Derivado de Plaquetas/química , Piel/efectos de los fármacos , Piel/metabolismo , Cicatrización de Heridas/efectos de los fármacosRESUMEN
There is increasing interest in the use of viruses as model systems for fundamental research and as templates for nanomaterials. In this work, the rodlike fd virus was subjected to chemical modifications targeting different solvent-exposed functional groups in order to tune its surface properties, especially reversing the surface charge from negative to positive. The carboxyl groups of fd were coupled with different kinds of organic amines by carbodiimide chemistry, resulting in modified viruses that are positively charged over a wide range of pH. Care was taken to minimize intervirus cross linking, which often occurs because of such modifications. The surface amino groups were also grafted with poly(ethylene glycol) (PEG) end-functionalized with an active succinimidyl ester in order to introduce a steric stabilization effect. By combining charge reversal with PEG grafting, a reversible attraction between positively and negatively charged PEG-grafted fd viruses could be realized, which was tuned by the ionic strength of the solution. In addition, a charge-reversed fd virus forms only a pure nematic phase in contrast to the cholesteric phase of the wild type. These modified viruses might be used as model systems in soft condensed matter physics, for example, in the study of polyelectrolyte complexes or lyotropic liquid-crystalline phase behavior.
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Virus/química , Electroforesis , Electroforesis en Gel de Poliacrilamida , Ésteres/química , Punto Isoeléctrico , Modelos Químicos , Nanoestructuras/química , Polietilenglicoles/química , Dispersión de Radiación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Propiedades de SuperficieRESUMEN
Artificial chaperones are of great interest in fighting protein misfolding and aggregation for the protection of protein bioactivity. A comprehensive understanding of the interaction between artificial chaperones and proteins is critical for the effective utilization of these materials in biomedicine. In this work, we fabricated three kinds of artificial chaperones with different surface charges based on mixed-shell polymeric micelles (MSPMs), and investigated their protective effect for lysozymes under thermal stress. It was found that MSPMs with different surface charges showed distinct chaperone-like behavior, and the neutral MSPM with PEG shell and PMEO2MA hydrophobic domain at high temperature is superior to the negatively and positively charged one, because of the excessive electrostatic interactions between the protein and charged MSPMs. The results may benefit to optimize this kind of artificial chaperone with enhanced properties and expand their application in the future.
Asunto(s)
Proteínas Aviares/química , Micelas , Chaperonas Moleculares/química , Muramidasa/química , Polietilenglicoles/química , Replegamiento Proteico , Animales , Pollos , Calor , Humanos , Desnaturalización ProteicaRESUMEN
Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(ß-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface-adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser-scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration.
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Antibacterianos/química , Biopelículas/efectos de los fármacos , Portadores de Fármacos/química , Micelas , Nanopartículas/química , Staphylococcaceae/efectos de los fármacos , Antibacterianos/farmacología , Portadores de Fármacos/farmacología , Liberación de Fármacos , Colorantes Fluorescentes/química , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Permeabilidad , Polietilenglicoles/química , Electricidad Estática , Propiedades de Superficie , Triclosán/química , Triclosán/farmacologíaRESUMEN
Lipase is active at the water-oil interface and thus very useful for many applications in non-aqueous media. However, the use of lipase is often limited due to the heat inactivation which is mainly caused by the irreversible aggregation among lipase molecules. The temperature-sensitive polymers can spontaneously form complexes with lipases at higher temperature in the confined spaces of the water in oil microemulsion. With cooling, lipases are released from the complexes and refold into the native state. In this way, the thermal stability of lipase in a microemulsion is effectively improved, and so is the stability of lipase at ambient temperature. Apart from proving the effectiveness and generality of this method, the temperature-sensitive polymers/lipase microemulsion represents a simple and efficient system which could be used in practical applications, since lipase retains the interfacial activity in this system. Moreover, the influences of some factors on the improvement are discussed and the mechanism of this method is suggested after exploring the process by dynamic light scattering and fluorescence measurements.
Asunto(s)
Lipasa/metabolismo , Aceites/química , Polímeros/química , Temperatura , Agua/química , Resinas Acrílicas/química , Candida/enzimología , Emulsiones , Estabilidad de Enzimas , Hidrodinámica , Espectrometría de FluorescenciaRESUMEN
Metallo-meso-5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrins (metallo-TPPSs), such as ZnTPPS, have been widely used as photosensitizers. However, their vulnerability to photodegradation significantly limits their applications. In this contribution, we demonstrate a method to enhance the photostability of metallo-TPPSs while retaining photoactivity via encapsulation inside cores of complex micelles. Poly(ethylene glycol)-b-poly(4-vinylpyridine) (PEG-b-P4VP) and metallo-TPPSs can form complex micelles in acidic solution through electrostatic interactions and then undergo axial coordination with the pyridine moieties of PEG-b-P4VP when the pH is adjusted to 7.4. In this way, metallo-TPPSs are entrapped in the hydrophobic, compact micellar cores, which effectively prevents photodegradation of the metallo-TPPSs that would otherwise occur in aqueous solution. In addition, the photodebromination of 2,3-dibromo-3-phenylpropionic acid (DPP) sensitized with ZnTPPS has been used as a model reaction to study the photosensitive activity of ZnTPPS entrapped in complex micelles. The entrapped ZnTPPSs exhibit pronounced activity and have much higher efficiency and faster photosensitive reaction rates than free ZnTPPS.
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Metaloporfirinas/farmacología , Micelas , Fármacos Fotosensibilizantes/farmacología , Polietilenglicoles/farmacología , Polímeros/farmacología , Polivinilos/farmacología , Luz , Metaloporfirinas/química , Fotoquímica , Polietilenglicoles/química , Polivinilos/química , Espectrofotometría UltravioletaRESUMEN
The synthesis and selected macroscopic properties of a new model system consisting of poly(N-isopropylacrylamide) (PNIPAM)-coated rod-like fd virus particles are presented. The sticky rod-like colloids can be used to study effect of particle shape on gelation transition, the structure and viscoelasticity of isotropic and nematic gels, and to make both open isotropic as well as ordered nematic particle networks. This model system of rod-like colloids, for which the strength of attraction between the particles is tunable, is obtained by chemically grafting highly monodisperse rod-like fd virus particles with thermoresponsive polymers, e.g. PNIPAM. At room temperature, suspensions of the resulting hybrid PNIPAM-fd are fluid sols which are in isotropic or liquid crystalline phases, depending on the particle concentration and ionic strength. During heating/cooling, the suspensions change reversibly between sol and gel state near a critical temperature of approximately 32 degrees C, close to the lower critical solution temperature of free PNIPAM. The so-called nematic gel, which exhibits a cholesteric feature, can therefore be easily obtained. The gelation behavior of PNIPAM-fd system and the structure of the nematic gel have been characterized by rheology, optical microscopy and small-angle X-ray scattering.