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1.
Acc Chem Res ; 56(13): 1826-1837, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37225704

RESUMEN

Functional ligands consist of a wide range of small or large molecules that exhibit a spectrum of physical, chemical, and biological properties. A suite of small molecules (e.g., peptides) or macromolecular ligands (e.g., antibodies and polymers) have been conjugated to particle surfaces for specific applications. However, postfunctionalization of ligands often presents challenges in controlling the surface density and may require the chemical modification of ligands. As an alternative option to postfunctionalization, our work has focused on using functional ligands as building blocks to assemble particles while maintaining their intrinsic (functional) properties. Through self-assembly or template-mediated assembly strategies, we have developed a range of protein-, peptide-, DNA-, polyphenol-, glycogen-, and polymer-based particles. This Account discusses the assembly of such nanoengineered particles, which includes self-assembled nanoparticles, hollow capsules, replica particles, and core-shell particles, according to three categories of functional ligands (i.e., small molecules, polymers, and biomacromolecules) that are used as building blocks for their formation. We discuss a range of covalent and noncovalent interactions among ligand molecules that have been explored to facilitate the assembly of particles. The physicochemical properties of the particles, including size, shape, surface charge, permeability, stability, thickness, stiffness, and stimuli-responsiveness, can be readily controlled by varying the ligand building block or by tuning the assembly method. By selecting specific ligands as building blocks, the bio-nano interactions (i.e., stealth, targeting, and cell trafficking) can also be modulated. For instance, particles composed mainly of low-fouling polymers (i.e., poly(ethylene glycol)) exhibit an extended blood circulation time (half-life > 12 h), while antibody-based nanoparticles demonstrate that a trade-off between stealth and targeting may be required when designing targeting nanoparticle systems. Small molecular ligands, such as polyphenols, have been used as building blocks for particle assembly as they can interact with various biomacromolecules through multiple noncovalent interactions, retain the function of biomacromolecules within the assembly, enable pH-responsive disassembly when coordinating with metal ions, and facilitate endosomal escape of nanoparticles. A perspective is provided on the current challenges associated with the clinical translation of ligand-based nanoparticles. This Account is also expected to serve as a reference to guide the fundamental research and development of functional particle systems assembled from various ligands for diverse applications.


Asunto(s)
Polietilenglicoles , Polímeros , Ligandos , Polímeros/química , Polietilenglicoles/química , Proteínas , Péptidos , Anticuerpos
2.
J Am Chem Soc ; 144(40): 18419-18428, 2022 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-36166420

RESUMEN

Surface modification with poly(ethylene glycol) (PEGylation) is an effective strategy to improve the colloidal stability of nanoparticles (NPs) and is often used to minimize cellular uptake and clearance of NPs by the immune system. However, PEGylation can also trigger the accelerated blood clearance (ABC) phenomenon, which is known to reduce the circulation time of PEGylated NPs. Herein, we report the engineering of stealth PEG NPs that can avoid the ABC phenomenon and, when modified with hyaluronic acid (HA), show specific cancer cell targeting and drug delivery. PEG NPs cross-linked with disulfide bonds are prepared by using zeolitic imidazolate framework-8 NPs as templates. The reported templating strategy enables the simultaneous removal of the template and formation of PEG NPs under mild conditions (pH 5.5 buffer). Compared to PEGylated liposomes, PEG NPs avoid the secretion of anti-PEG antibodies and the presence of anti-PEG IgM and IgG did not significantly accelerate the blood clearance of PEG NPs, indicating the inhibition of the ABC effect for the PEG NPs. Functionalization of the PEG NPs with HA affords PEG NPs that retain their stealth properties against macrophages, target CD44-expressed cancer cells and, when loaded with the anticancer drug doxorubicin, effectively inhibit tumor growth. The innovation of this study lies in the engineering of PEG NPs that can circumvent the ABC phenomenon and that can be functionalized for the improved and targeted delivery of drugs.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Antineoplásicos/química , Disulfuros , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Ácido Hialurónico/química , Inmunoglobulina G , Inmunoglobulina M/uso terapéutico , Liposomas , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Polietilenglicoles/química
3.
Biomacromolecules ; 22(2): 612-619, 2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33337863

RESUMEN

Poly(ethylene glycol) (PEG) is well known to endow nanoparticles (NPs) with low-fouling and stealth-like properties that can reduce immune system clearance in vivo, making PEG-based NPs (particularly sub-100 nm) of interest for diverse biomedical applications. However, the preparation of sub-100 nm PEG NPs with controllable size and morphology is challenging. Herein, we report a strategy based on the noncovalent coordination between PEG-polyphenolic ligands (PEG-gallol) and transition metal ions using a water-in-oil microemulsion phase to synthesize sub-100 nm PEG NPs with tunable size and morphology. The metal-phenolic coordination drives the self-assembly of the PEG-gallol/metal NPs: complexation between MnII and PEG-gallol within the microemulsions yields a series of metal-stabilized PEG NPs, including 30-50 nm solid and hollow NPs, depending on the MnII/gallol feed ratio. Variations in size and morphology are attributed to the changes in hydrophobicity of the PEG-gallol/MnII complexes at varying MnII/gallol ratios based on contact angle measurements. Small-angle X-ray scattering analysis, which is used to monitor the particle size and intermolecular interactions during NP evolution, reveals that ionic interactions are the dominant driving force in the formation of the PEG-gallol/MnII NPs. pH and cytotoxicity studies, and the low-fouling properties of the PEG-gallol/MnII NPs confirm their high biocompatibility and functionality, suggesting that PEG polyphenol-metal NPs are promising systems for biomedical applications.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Polietilenglicoles
4.
Appl Microbiol Biotechnol ; 105(4): 1435-1446, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33484319

RESUMEN

In this study, we applied metabolic engineering and bioprocessing strategies to enhance heterologous production of an important biodegradable copolymer, i.e., poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), with a modulated 3-hydroxyvalerate (3-HV) monomeric fraction from structurally unrelated carbon of glycerol in engineered Escherichia coli under different oxygenic conditions. We used our previously derived propanologenic (i.e., 1-propanol-producing) E. coli strain with an activated genomic Sleeping beauty mutase (Sbm) operon as a host for heterologous expression of the phaCAB operon. The 3-HV monomeric fraction was modulated by regulating dissimilated carbon flux channeling from the tricarboxylic acid (TCA) cycle into the Sbm pathway for biosynthesis of propionyl-CoA, which is a key precursor to (R)-3-hydroxyvaleryl-CoA (3-HV-CoA) monomer. The carbon flux channeling was regulated either by manipulating a selection of genes involved in the TCA cycle or varying oxygenic condition of the bacterial culture. With these consolidated strategies being implemented, we successfully achieved high-level PHBV biosynthesis with a wide range of 3-HV monomeric fraction from ~ 4 to 50 mol%, potentially enabling the fine-tuning of PHBV mechanical properties at the biosynthesis stage. We envision that similar strategies can be applied to enhance bio-based production of chemicals derived from succinyl-CoA. KEY POINTS: • TCA cycle engineering was applied to enhance 3-HV monomeric fraction in E. coli. • Effects of oxygenic conditions on 3-HV incorporation into PHBV in E. coli were investigated. • Bacterial cultivation for high-level PHBV production in engineered E. coli was performed.


Asunto(s)
Escherichia coli , Hidroxibutiratos , Escherichia coli/genética , Ácidos Pentanoicos , Poliésteres
5.
J Nanobiotechnology ; 19(1): 448, 2021 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-34952588

RESUMEN

BACKGROUND: Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus (V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse. METHODS: Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 â„ƒ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules. RESULTS: DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed. CONCLUSION: Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.


Asunto(s)
Antiinfecciosos/uso terapéutico , Nanogeles/uso terapéutico , Vibriosis/tratamiento farmacológico , Animales , Antiinfecciosos/química , Antiinfecciosos/metabolismo , Antiinfecciosos/farmacología , Artemia/microbiología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Carbono/química , Dextranos/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Hepatopáncreas/patología , Nanogeles/química , Nanogeles/toxicidad , Toxinas Biológicas/química , Toxinas Biológicas/metabolismo , Vibriosis/prevención & control , Vibriosis/veterinaria , Vibrio parahaemolyticus/efectos de los fármacos , Vibrio parahaemolyticus/patogenicidad
6.
Int J Mol Sci ; 22(11)2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34063782

RESUMEN

In this study, we demonstrate the synthesis of carbonized nanogels (CNGs) from an amino acid (lysine hydrochloride) using a simple pyrolysis method, resulting in effective viral inhibition properties against infectious bronchitis virus (IBV). The viral inhibition of CNGs was studied using both in vitro (bovine ephemeral fever virus (BEFV) and pseudorabies virus (PRV)) and in ovo (IBV) models, which indicated that the CNGs were able to prevent virus attachment on the cell membrane and penetration into the cell. A very low concentration of 30 µg mL-1 was found to be effective (>98% inhibition) in IBV-infected chicken embryos. The hatching rate and pathology of IBV-infected chicken embryos were greatly improved in the presence of CNGs. CNGs with distinctive virus-neutralizing activities show great potential as a virostatic agent to prevent the spread of avian viruses and to alleviate the pathology of infected avian species.


Asunto(s)
Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Virus de la Bronquitis Infecciosa/efectos de los fármacos , Lisina/farmacología , Nanogeles/administración & dosificación , Sustancias Protectoras/farmacología , Animales , Línea Celular , Pollos/virología , Chlorocebus aethiops , Infecciones por Coronavirus/virología , Cricetinae , Virus de la Fiebre Efímera Bovina/efectos de los fármacos , Femenino , Herpesvirus Suido 1/efectos de los fármacos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/virología , Ratas , Ratas Sprague-Dawley , Células Vero , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
7.
Eur J Cancer Care (Engl) ; 29(4): e13243, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32510671

RESUMEN

OBJECTIVE: Head and neck cancer (HNC) patients suffer from symptoms and fear of recurrence (FoR), which both affect their quality of life (QoL). Based on a self-regulation model, the purpose of the study was to examine patients' FoR as a mediator of the relation between symptoms and QoL, and to identify which symptoms may trigger FoR. METHODS: A cross-sectional study was conducted, using convenience sampling. Structured questionnaires were used to collect data at a medical centre in Northern Taiwan. The analytic methods included descriptive statistics, structural equation modelling and linear regression. RESULTS: A total of 103 participants were recruited. Patients experienced a medium level of symptom severity and QoL but a moderate to high level of FoR. Symptom severity, FoR and QoL were significantly correlated. FoR was a significant partial mediator between symptom severity and QoL. The significant factors of the overall FoR and the subscale of health worry were "pain in general" and "pain in the mouth, throat or neck." "Pain in general" was a significant factor for the subscale of cancer worry. CONCLUSIONS: This theory-driven study supports a mediation model of FoR among HNC patients and provides a more comprehensive understanding of the antecedents and consequences of FoR.


Asunto(s)
Trastornos de Deglución/fisiopatología , Disnea/fisiopatología , Miedo/psicología , Neoplasias de Cabeza y Cuello/fisiopatología , Náusea/fisiopatología , Recurrencia Local de Neoplasia/psicología , Dolor/fisiopatología , Calidad de Vida , Anciano , Comunicación , Femenino , Neoplasias de Cabeza y Cuello/psicología , Humanos , Masculino , Análisis de Mediación , Persona de Mediana Edad , Autocontrol , Taiwán
8.
Biomacromolecules ; 20(9): 3592-3600, 2019 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-31448896

RESUMEN

Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g-1) when compared with the PEG (3% ID g-1) and PEG-RDG (7% ID g-1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems.


Asunto(s)
Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Oligopéptidos/farmacología , Polietilenglicoles/farmacología , Animales , Línea Celular Tumoral , Citoplasma/efectos de los fármacos , Endocitosis/efectos de los fármacos , Humanos , Ligandos , Oligopéptidos/química , Polietilenglicoles/química , Transducción de Señal/efectos de los fármacos , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Propiedades de Superficie
9.
Small ; 14(39): e1802342, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30156378

RESUMEN

Interfacial self-assembly is a powerful organizational force for fabricating functional nanomaterials, including nanocarriers, for imaging and drug delivery. Herein, the interfacial self-assembly of pH-responsive metal-phenolic networks (MPNs) on the liquid-liquid interface of oil-in-water emulsions is reported. Oleic acid emulsions of 100-250 nm in diameter are generated by ultrasonication, to which poly(ethylene glycol) (PEG)-based polyphenolic ligands are assembled with simultaneous crosslinking by metal ions, thus forming an interfacial MPN. PEG provides a protective barrier on the emulsion phase and renders the emulsion low fouling. The MPN-coated emulsions have a similar size and dispersity, but an enhanced stability when compared with the uncoated emulsions, and exhibit a low cell association in vitro, a blood circulation half-life of ≈50 min in vivo, and are nontoxic to healthy mice. Furthermore, a model anticancer drug, doxorubicin, can be encapsulated within the emulsion phase at a high loading capacity (≈5 fg of doxorubicin per emulsion particle). The MPN coating imparts pH-responsiveness to the drug-loaded emulsions, leading to drug release at cell internalization pH and a potent cell cytotoxicity. The results highlight a straightforward strategy for the interfacial nanofabrication of pH-responsive emulsion-MPN systems with potential use in biomedical applications.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Nanoestructuras/química , Animales , Doxorrubicina/química , Concentración de Iones de Hidrógeno , Ratones , Ácido Oléico/química , Polietilenglicoles/química
10.
Langmuir ; 34(37): 10817-10827, 2018 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-30132674

RESUMEN

The assembly of particles composed solely or mainly of poly(ethylene glycol) (PEG) is an emerging area that is gaining increasing interest within bio-nano science. PEG, widely considered to be the "gold standard" among polymers for drug delivery, is providing a platform for exploring fundamental questions and phenomena at the interface between particle engineering and biomedicine. These include the targeting and stealth behaviors of synthetic nanomaterials in biological environments. In this feature article, we discuss recent work in the nanoengineering of PEG particles and explore how they are enabling improved targeting and stealth performance. Specific examples include PEG particles prepared through surface-initiated polymerization, mesoporous silica replication via postinfiltration, and particle assembly through metal-phenolic coordination. This particle class exhibits unique in vivo behavior (e.g., biodistribution and immune cell interactions) and has recently been explored for drug delivery applications.


Asunto(s)
Portadores de Fármacos/química , Nanopartículas/química , Polietilenglicoles/química , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Doxorrubicina/farmacología , Humanos , Nanotecnología/métodos , Compuestos Organoplatinos/farmacología , Tamaño de la Partícula , Polimerizacion , Profármacos/farmacología
11.
Bioconjug Chem ; 28(7): 1859-1866, 2017 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-28548819

RESUMEN

Particle-cell interactions are governed by, among other factors, the composition and surface properties of the particles. Herein, we report the preparation of various polymer capsules with different compositions and properties via atom transfer radical polymerization mediated continuous assembly of polymers (CAPATRP), where the cellular interactions of these capsules, particularly fouling and specific targeting, are examined by flow cytometry and deconvolution microscopy. Acrylated eight-arm poly(ethylene glycol) (8-PEG) and poly(N-(2-hydroxypropyl)-methacrylamide) (PHPMA) as well as methacrylated hyaluronic acid (HA), poly(glutamic acid) (PGA), and poly(methacrylic acid) (PMA) are used as macro-cross-linkers to obtain a range of polymer capsules with different compositions (PEG, PHPMA, HA, PGA, and PMA). Capsules composed of low-fouling polymers, PEG and PHPMA, show negligible association with macrophage Raw 264.7, monocyte THP-1, and HeLa cells. HA capsules, although moderately low-fouling (<22%) to HeLa, BT474, Raw 264.7, and THP-1 cells, exhibit high targeting specificity to CD44-over-expressing MDA-MB-231 cells. In contrast, PGA and PMA capsules show high cellular association toward phagocytic Raw 264.7 and THP-1 cells. These findings demonstrate the capability of the CAPATRP technique in preparing polymer capsules with specific cellular interactions.


Asunto(s)
Membrana Celular/metabolismo , Polímeros/química , Animales , Cápsulas/síntesis química , Cápsulas/química , Cápsulas/metabolismo , Reactivos de Enlaces Cruzados/química , Citometría de Flujo , Células HeLa , Humanos , Ratones , Microscopía , Polímeros/síntesis química , Polímeros/metabolismo , Células RAW 264.7 , Propiedades de Superficie
12.
Angew Chem Int Ed Engl ; 56(29): 8510-8515, 2017 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-28582605

RESUMEN

A bioactive synthetic porous shell was engineered to enable cells to survive in an oligotrophic environment. Eukaryotic cells (yeast) were firstly coated with a ß-galactosidase (ß-gal), before crystallization of a metal-organic framework (MOF) film on the enzyme coating; thereby producing a bioactive porous synthetic shell. The ß-gal was an essential component of the bioactive shell as it generated nutrients (that is, glucose and galactose) required for cell viability in nutrient-deficient media (lactose-based). Additionally, the porous MOF coating carried out other vital functions, such as 1) shielding the cells from cytotoxic compounds and radiation, 2) protecting the non-native enzymes (ß-gal in this instance) from degradation and internalization, and 3) allowing for the diffusion of molecules essential for the survival of the cells. Indeed, this bioactive porous shell enabled the survival of cells in simulated extreme oligotrophic environments for more than 7 days, leading to a decrease in cell viability less than 30 %, versus a 99 % decrease for naked yeast. When returned to optimal growth conditions the bioactive porous exoskeleton could be removed and the cells regained full growth immediately. The construction of bioactive coatings represents a conceptually new and promising approach for the next-generation of cell-based research and application, and is an alternative to synthetic biology or genetic modification.


Asunto(s)
Células Artificiales/metabolismo , Estructuras Metalorgánicas/metabolismo , beta-Galactosidasa/metabolismo , Células Artificiales/química , Supervivencia Celular , Estructuras Metalorgánicas/química , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo , beta-Galactosidasa/química
13.
Biomacromolecules ; 17(6): 2268-76, 2016 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-27249228

RESUMEN

We engineered metal-phenolic capsules with both high targeting and low nonspecific cell binding properties. The capsules were prepared by coating phenolic-functionalized hyaluronic acid (HA) and poly(ethylene glycol) (PEG) on calcium carbonate templates, followed by cross-linking the phenolic groups with metal ions and removing the templates. The incorporation of HA significantly enhanced binding and association with a CD44 overexpressing (CD44+) cancer cell line, while the incorporation of PEG reduced nonspecific interactions with a CD44 minimal-expressing (CD44-) cell line. Moreover, high specific targeting to CD44+ cells can be balanced with low nonspecific binding to CD44- cells simply by using an optimized feed-ratio of HA and PEG to vary the content of HA and PEG incorporated into the capsules. Loading an anticancer drug (i.e., doxorubicin) into the obtained capsules resulted in significantly higher cytotoxicity to CD44+ cells but lower cytotoxicity to CD44- cells.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Cápsulas/administración & dosificación , Doxorrubicina/farmacología , Ácido Hialurónico/química , Metales/química , Nanopartículas/administración & dosificación , Polietilenglicoles/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cápsulas/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Diseño de Fármacos , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Nanopartículas/química , Células Tumorales Cultivadas
14.
Biomacromolecules ; 16(3): 807-14, 2015 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-25654404

RESUMEN

Metal-phenolic coordination chemistry provides a simple and rapid way to fabricate ultrathin films. Here, we report a facile strategy for the preparation of low-fouling and pH-degradable metal-phenolic network (MPN) capsules using a synthetic polyphenol derivative, poly(ethylene glycol) (PEG)-polyphenol, as a building block. PEG-MPN capsules exhibit reduced nonspecific protein adsorption and cell association compared with tannic acid (TA)-MPN capsules. In addition, they show faster disassembly at a biologically relevant pH (5) than TA-MPN capsules (80% in 5 h vs 30% in 10 days). PEG-MPN capsules combine both the low fouling properties of PEG and the advantages of the MPN-driven assembly process (e.g., fast assembly and pH-degradability).


Asunto(s)
Incrustaciones Biológicas , Portadores de Fármacos/química , Polietilenglicoles/química , Polifenoles/química , Adsorción , Proteínas Sanguíneas/química , Complejos de Coordinación/química , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Hierro/química
15.
Soft Matter ; 10(15): 2656-63, 2014 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-24647351

RESUMEN

We report a versatile approach for the design of substrate-independent low-fouling surfaces via mussel-inspired immobilisation of zwitterionic peptides. Using mussel-inspired polydopamine (PDA) coatings, zwitterionic glutamic acid- and lysine-based peptides were immobilised on various substrates, including noble metals, metal oxides, polymers, and semiconductors. The variation of surface chemistry and surface wettability upon surface treatment was monitored with X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Following peptide immobilisation, the surfaces became more hydrophilic due to the strong surface hydration compared with PDA-coated surfaces. The peptide-functionalised surfaces showed resistance to human blood serum adsorption and also effectively prevented the adhesion of gram-negative and gram-positive bacteria (i.e., Escherichia coli and Staphylococcus epidermidis) and mammalian cells (i.e., NIH 3T3 mouse embryonic fibroblast cells). The versatility of mussel-inspired chemistry combined with the unique biological nature and tunability of peptides allows for the design of low-fouling surfaces, making this a promising coating technique for various applications.


Asunto(s)
Indoles/química , Péptidos/química , Polímeros/química , Adsorción , Secuencia de Aminoácidos , Animales , Adhesión Bacteriana , Adhesión Celular , Escherichia coli/fisiología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas Inmovilizadas/química , Proteínas Inmovilizadas/metabolismo , Ratones , Células 3T3 NIH , Suero/química , Staphylococcus epidermidis/fisiología , Propiedades de Superficie
16.
Chem Commun (Camb) ; 60(19): 2591-2604, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38285062

RESUMEN

Poly(ethylene glycol) (PEG) is considered to be the "gold standard" among the stealth polymers employed for drug delivery. Using PEG to modify or engineer particles has thus gained increasing interest because of the ability to prolong blood circulation time and reduce nonspecific biodistribution of particles in vivo, owing to the low fouling and stealth properties of PEG. In addition, endowing PEG-based particles with targeting and drug-loading properties is essential to achieve enhanced drug accumulation at target sites in vivo. In this feature article, we focus on recent work on the synthesis of PEG particles, in which PEG is the main component in the particles. We highlight different synthesis methods used to generate PEG particles, the influence of the physiochemical properties of PEG particles on their stealth and targeting properties, and the application of PEG particles in targeted drug delivery.


Asunto(s)
Sistemas de Liberación de Medicamentos , Polietilenglicoles , Polietilenglicoles/química , Distribución Tisular , Polímeros , Ingeniería , Portadores de Fármacos/química
17.
J Mater Chem B ; 12(22): 5391-5404, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38716492

RESUMEN

Quercetin, a flavonoid abundantly found in onions, fruits, and vegetables, is recognized for its pharmacological potential, especially for its anticoagulant properties that work by inhibiting thrombin and coagulation factor Xa. However, its clinical application is limited due to poor water solubility and bioavailability. To address these limitations, we engineered carbonized nanogels derived from quercetin (CNGsQur) using controlled pyrolysis and polymerization techniques. This led to substantial improvements in its anticoagulation efficacy, water solubility, and biocompatibility. We generated a range of CNGsQur by subjecting quercetin to varying pyrolytic temperatures and then assessed their anticoagulation capacities both in vitro and in vivo. Coagulation metrics, including thrombin clotting time (TCT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), along with a rat tail bleeding assay, were utilized to gauge the efficacy. CNGsQur showed a pronounced extension of coagulation time compared to uncarbonized quercetin. Specifically, CNGsQur synthesized at 270 °C (CNGsQur270) exhibited the most significant enhancement in TCT, with a binding affinity to thrombin exceeding 400 times that of quercetin. Moreover, variants synthesized at 310 °C (CNGsQur310) and 290 °C (CNGsQur290) showed the most substantial delays in PT and aPTT, respectively. Our findings indicate that the degree of carbonization significantly influences the transformation of quercetin into various CNGsQur forms, each affecting distinct coagulation pathways. Additionally, both intravenous and oral administrations of CNGsQur were found to extend rat tail bleeding times by up to fivefold. Our studies also demonstrate that CNGsQur270 effectively delays and even prevents FeCl3-induced vascular occlusion in a dose-dependent manner in mice. Thus, controlled pyrolysis offers an innovative approach for generating quercetin-derived CNGs with enhanced anticoagulation properties and water solubility, revealing the potential for synthesizing self-functional carbonized nanomaterials from other flavonoids for diverse biomedical applications.


Asunto(s)
Anticoagulantes , Quercetina , Quercetina/química , Quercetina/farmacología , Anticoagulantes/química , Anticoagulantes/farmacología , Animales , Ratas , Coagulación Sanguínea/efectos de los fármacos , Nanogeles/química , Humanos , Ratones , Masculino , Ratas Sprague-Dawley , Tamaño de la Partícula
18.
Protein Expr Purif ; 89(2): 219-24, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23583309

RESUMEN

Purple membrane (PM) is a part of cytoplasmic membrane in certain extreme halophilic microorganisms belonging to Domain Archaea. It transduces light energy to generate proton gradient for ATP synthesis in the microorganisms. Bacteriorhodopsin (BR) is the only protein in PM responsible for the generation of proton gradient. Generally, PM was purified from Halobacterium salinarum via a tedious and lengthy sucrose density gradient ultracentrifugation (SGU). In this work, a facile method based on polyethyleneglycol (PEG)-phosphate aqueous-two- phase extraction system (ATPS) was employed to purify PM from cell lysate of H. salinarum. The results showed that PM could be completely recovered from the interface of PEG-phosphate ATPS with BR purity ca 94.1% as measured by UV-visible absorption spectra. In comparison with PM obtained by SGU, the PM isolated by ATPS could achieve the same level of purity and photocurrent activity (ca 177.2nA/µgBR/cm(2)) as analyzed by SDS-PAGE and photocurrent measurement, respectively. The easily scalable and straightforward ATPS procedure demonstrated that PM can be purified and recovered more cost-effectively with a significantly reduced operation time that should lead to broader range applications of PM possible.


Asunto(s)
Proteínas Arqueales/aislamiento & purificación , Proteínas Arqueales/metabolismo , Bacteriorodopsinas/aislamiento & purificación , Bacteriorodopsinas/metabolismo , Halobacterium salinarum/metabolismo , Membrana Púrpura/metabolismo , Fraccionamiento Celular , Electroforesis en Gel de Poliacrilamida , Diseño de Equipo , Halobacterium salinarum/química , Fosfatos/química , Fotoquímica/instrumentación , Polietilenglicoles/química , Membrana Púrpura/química , Ultracentrifugación
19.
Zhongguo Gu Shang ; 36(7): 623-7, 2023 Jul 25.
Artículo en Zh | MEDLINE | ID: mdl-37475625

RESUMEN

OBJECTIVE: To explore the clinical efficacy of percutaneous vertebroplasty(PVP) combined with nerve block in the treatment of lumbar osteoporotic vertebral compression fractures under the guidance of traditional chinese medicine "theory of equal emphasis on muscle and bone". METHODS: Total of 115 patients with lumbar osteoporotic vertebral compression fractures were treated by percutaneous vertebroplasty from January 2015 to March 2022, including 51 males and 64 females, aged 25 to 86 (60.5±15.9) years. Among them, 48 cases were treated with PVP operation combined with erector spinae block and joint block of the injured vertebral articular eminence (intervention group), and 67 cases were treated with conventional PVP operation (control group). The visual analogue scale(VAS) and Oswestry disability index(ODI) before operation, 3 days, 1 month and 6 months after operation between two groups were evaluated. The operation time, number of punctures and intraoperative bleeding between two groups were compared. RESULTS: The VAS and ODI scores of both groups improved significantly after operation compared with those before operation(P<0.05). Moreover, the VAS and ODI scores of 3 days and 1 month after operation of the intervention group improved more significantly than that of the control group(P<0.05). The difference of VAS and ODI scores before operation and 6 months after operation between two groups had no statistical significances(P>0.05). There was no statistically significant difference in the number of punctures and intraoperative bleeding between the two groups (P>0.05). CONCLUSION: Based on the theory of "equal emphasis on muscles and bones", PVP combined with nerve block can effectively relieve paravertebral soft tissue spasm and other "muscle injuries", which can significantly improve short-term postoperative low back pain and lumbar spine mobility compared to conventional PVP treatment, and accelerate postoperative recovery, resulting in satisfactory clinical outcomes.


Asunto(s)
Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Masculino , Femenino , Humanos , Fracturas por Compresión/cirugía , Vertebroplastia/métodos , Fracturas de la Columna Vertebral/cirugía , Punción Espinal , Vértebras Lumbares/cirugía , Vértebras Lumbares/lesiones , Músculos , Resultado del Tratamiento , Fracturas Osteoporóticas/cirugía , Estudios Retrospectivos , Cementos para Huesos
20.
Zhongguo Gu Shang ; 36(9): 859-65, 2023 Sep 25.
Artículo en Zh | MEDLINE | ID: mdl-37735079

RESUMEN

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T2 fracture, 1 case of T3 fracture, 3 cases of T4 fracture, 3 cases of T5 fracture, and 7 cases of T6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T1 fracture, 5 cases of T4 fracture, 2 cases of T5 fracture and 9 cases of T6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION: Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.


Asunto(s)
Fracturas Osteoporóticas , Robótica , Femenino , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Fracturas Osteoporóticas/cirugía , Pérdida de Sangre Quirúrgica , Cementos para Huesos , Estudios Retrospectivos , Vértebras Torácicas/cirugía
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