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1.
Int J Biol Macromol ; 232: 123412, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-36706883

RESUMEN

Disruption of cellular homeostasis by the aggregation of polyglutamine (polyQ) in the huntingtin protein (Htt) leads Huntington's disease (HD). Effective drugs for treating HD have not been developed, as the molecular mechanism underlying HD pathogenesis remains unclear. To develop strategies for inhibiting HD pathogenesis, the intermolecular interaction of Htt with IP3 receptor 1 (IP3R1) was investigated. Peptide (termed ICT60) corresponding to a coiled-coil motif in the C-terminus of IP3R1 was designed. Several biophysical approaches revealed the strong and specific binding of ICT60 to the N-terminal part of HttEx1. ICT60 inhibited not only amyloid formation by HttEx1, but also the cytotoxicity and cell-penetration ability of the amyloid fibrils of HttEx1. The importance of coiled-coil structure was verified by charge-manipulated variants. The coiled-coil structures of ICT60-KK and -EE were partially and largely disrupted, respectively. ICT60 wild-type and -KK inhibited amyloid formation by HttEx1-46Q, whereas ICT60-EE did not block amyloidogenesis. Similarly, the cytotoxicity and cell-penetration ability of the amyloid fibrils of HttEx1-46Q were efficiently inhibited by ICT60 wild-type and ICT60-KK, but not by ICT60-EE. We propose a mechanical model explaining how an IP3 receptor-inspired molecule can modulate cytotoxic amyloid formation by Htt, providing a molecular basis for developing therapeutics to treat HD.


Asunto(s)
Amiloide , Amiloide/química , Exones , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Dominios Proteicos
2.
Int J Nanomedicine ; 17: 6221-6231, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36531114

RESUMEN

Introduction: A recombinant protein cannot induce sufficient immune response by itself. Various substances, including cytokine and mineral, have been used as adjuvants to enhance the immunogenicity and efficacy of vaccines; however, most of them induce excessive immune responses or exhibit cytotoxicity. In this study, a self-emulsifying drug delivery system (SEDDS), an isotropic mixture of oil, surfactant, and solvent, was designed for oil-in-water emulsions as a non-toxic adjuvant to increase immune response to antigens. Methods: Squalene-based oil-in-water emulsions were prepared by SEDDS to assess its value as an adjuvant. Fifteen emulsions (F1-F15) were prepared by stirring two types of surfactants (Span® 85 and Kolliphor® RH40), and squalene and carboxymethyl cellulose (CMC) were added at different ratios. The physical properties and viscosity of the 15 emulsions were evaluated by measuring droplet size, zeta potential, and polydispersity index. The toxic effect of emulsions was assessed by acute toxicity test in mice. Mice were immunized twice with 1:1 mixtures of antigen and adjuvant (15 emulsions, phosphate-buffered saline, and commercial alum-based adjuvant). Antigen-specific antibody titers from immunized mice serum were measured by an indirect enzyme-linked immunosorbent assay. Results: All emulsions exhibited droplet sizes ranging from 322 to 812 nm and maintained zeta potential values between -30 mV to -10 mV for 4 weeks, indicating good physical stability as a vaccine adjuvant. Additionally, all emulsions were non-toxic, and they induced humoral immunity at a similar level compared to commercial alum-based adjuvant in the first immunization. However, 12% squalene-based oil-in-water emulsion containing 0.5% of ultra-high viscosity CMC (F15) showed significantly higher immune response than a commercial adjuvant in the second immunization. Conclusion: Squalene-based oil-in-water emulsions could be conveniently prepared using SEDDS technique and are non-toxic and stable at room temperature storage. Moreover, squalene-based oil-in-water emulsions show enhanced immune induction with antigen; hence, they can possibly be used as effective adjuvants.


Asunto(s)
Adyuvantes Inmunológicos , Escualeno , Ratones , Animales , Emulsiones , Adyuvantes Inmunológicos/farmacología , Antígenos , Sistemas de Liberación de Medicamentos , Tensoactivos , Agua
3.
Molecules ; 27(24)2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36557850

RESUMEN

Leuprolide is a synthetic nonapeptide drug (pyroGlu-His-Trp-Ser-Tyr-d-Leu-Leu-Arg-Pro-NHEt) that acts as a gonadotropin-releasing hormone agonist. The continuous administration of therapeutic doses of leuprolide inhibits gonadotropin secretion, which is used in androgen-deprivation therapy for the treatment of advanced prostate cancer, central precocious puberty, endometriosis, uterine fibroids, and other sex-hormone-related conditions. To improve the pharmacokinetic properties of peptide drugs, a fatty acid was conjugated with leuprolide for long-term action. In this study, we developed a simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of leuprolide and leuprolide-oleic acid conjugate (LOC) levels. The developed method was validated in terms of linearity, precision, accuracy, recovery, matrix effect, and stability according to the US Food and Drug Administration guidelines, and the parameters were within acceptable limits. Subsequently, the pharmacokinetics of leuprolide and LOCs were evaluated. In vivo rat subcutaneous studies revealed that conjugation with fatty acids significantly altered the pharmacokinetics of leuprolide. After the subcutaneous administration of fatty-acid-conjugated leuprolide, the mean absorption time and half-life were prolonged. To the best of our knowledge, this is the first study showing the effects of fatty acid conjugates on the pharmacokinetics of leuprolide using a newly developed UPLC-MS/MS method for the simultaneous quantification of leuprolide and LOCs.


Asunto(s)
Leuprolida , Neoplasias de la Próstata , Masculino , Humanos , Femenino , Ratas , Animales , Cromatografía Liquida/métodos , Leuprolida/farmacocinética , Espectrometría de Masas en Tándem/métodos , Ácidos Grasos , Antagonistas de Andrógenos , Cromatografía Líquida de Alta Presión
4.
Int J Nanomedicine ; 17: 2243-2260, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35615542

RESUMEN

Purpose: To conjugate different degree of saturation of C18 fatty acids (stearic acid, oleic acid, and linoleic acid) with the hydroxyl groups of leuprolide acetate (LEU acetate) and to investigate the controlled release and enhanced permeability through self-assembled nanoparticles (L18FNs). Methods: Yamaguchi esterification with benzoyl chloride and DMAP (4-Dimethylaminopyridine) allowed the conjugation of the fatty acid to the hydroxyl group of LEU. The three conjugates were then designated as stearic acid-conjugated LEU, LSC, oleic acid-conjugated LEU, LOC, and linoleic acid-conjugated LEU, LLC, respectively. The conjugates (L18FCs) were purified using preparative HPLC (Prep-HPLC) and identified through various instrumental analyses. Results: The zeta potential, particle size, and morphology of each L18FNs were evaluated. In the case of LSNs, the zeta potential value was relatively low and the particle size was larger than LONs and LLNs owing to the higher hydrophobicity of saturated fatty chain, while the LLNs showed a higher zeta potential and smaller particle size. In human plasma, LLC showed the fastest degradation rate with the highest accumulative drug release. The permeability of L18FNs was analyzed through the Franz diffusion cell experiment, confirming that the degree of saturation of fatty acids affects the permeability of LFNs. While the permeability of LSNs was not significantly enhanced due to higher particle size after nanonization, LONs and LLNs increased 1.56 and 1.85 times in permeation, respectively, compared to LEU. Conclusion: Utilization of different degree of saturation of fatty acids to conjugate a peptide drug could provide pharmaceutical versatility via self-assembly and modification of physicochemical properties.


Asunto(s)
Ácidos Grasos , Nanopartículas , Ácidos Grasos/química , Humanos , Ácido Linoleico , Nanopartículas/química , Ácido Oléico/química , Péptidos , Ácidos Esteáricos
5.
Data Brief ; 42: 108137, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35496475

RESUMEN

Zinc oxide (ZnO) nanoparticles (NPs) have been applied as high-performance intelligent materials to create a hierarchical multimodal-porous architectures for application in biomedical research fields [1]. They were microfluidically synthesized via dual-step nanofabrication compared to the conventional particles including ZnO NPs synthesized at single-pot macroscale, nanosized ZnO, and hybrid ZnO. The physicochemical properties were characterized, including morphology, particle size distribution, atomic composition, crystallinity, purity, reactant viscosity, surface charge, photocatalysis, photoluminescence, and porosity. A hierarchical multimodal-porous three-dimensional (3D) architecture of ZnO NPs was generated and optimized on the solid plate substrate of cellulose paper sheet after solvent evaporation. The dataset provides the nanomaterial design and architecture generation of ZnO NPs, explaining multi-physics phenomena in association with performance optimization processes.

6.
Pharmaceuticals (Basel) ; 14(6)2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34073760

RESUMEN

Circadian dysfunction is closely associated with an increased risk of various diseases. Considering that molecular clock machinery serves as an intrinsic time-keeping system underlying the circadian rhythm of biological processes, the modulation of the molecular clock machinery is an attractive therapeutic target with novel mechanisms of action. Based on the previous structure-activity relationship study of small molecule cryptochrome (CRY) inhibitors possessing an ethoxypropanoic acid moiety, non-ethoxypropanoic acid-type inhibitors have been developed by bioisosteric replacement. They were evaluated as potent and effective enhancers of E-box-mediated transcription, and, in particular, ester 5d and its hydrolysis product 2d exhibited desirable metabolic and pharmacokinetic profiles as promising drug candidates. Compound 2d directly bound to both CRY1 and 2 in surface plasmon resonance analyses, suggesting that the molecular target is CRY. Effects of compound 5d and 2d on suppressive action of CRY1 on CLOCK:BMAL1-activated E-box-LUC reporter activity revealed that both compounds inhibited the negative feedback actions of CRY on CLOCK:BMAL1. Most importantly, compounds 5d and 2d exhibited significant effects on molecular circadian rhythmicity to be considered circadian clock-enhancers, distinct from the previously developed CRY inhibitors possessing an ethoxypropanoic acid moiety.

7.
Pharmaceutics ; 13(2)2021 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-33561936

RESUMEN

Antimicrobial activity of multiscale metal oxide (MO) particles against Escherichia coli (E. coli) and M13 bacteriophage (phage) was investigated under dual ultraviolet (UV) irradiation. Zinc oxide (ZnO), magnesium oxide (MgO), cuprous oxide (Cu2O), and cupric oxide (CuO) were selected as photocatalytic antimicrobials in MO particles. Physicochemical properties including morphology, particle size/particle size distribution, atomic composition, crystallinity, and porosity were evaluated. Under UV-A and UV-C irradiation with differential UV-C intensities, the antimicrobial activity of MO particles was monitored in E. coli and phage. MO particles had nano-, micro- and nano- to microscale sizes with irregular shapes, composed of atoms as ratios of chemical formulae and presented crystallinity as pure materials. They had wide-range specific surface area levels of 0.40-46.34 m2/g. MO particles themselves showed antibacterial activity against E. coli, which was the highest among the ZnO particles. However, no viral inactivation by MO particles occurred in phage. Under dual UV irradiation, multiscale ZnO and CuO particles had superior antimicrobial activities against E. coli and phage, as mixtures of nano- and microparticles for enhanced photocatalytic antimicrobials. The results showed that the dual UV-multiscale MO particle hybrids exhibit enhanced antibiotic potentials. It can also be applied as a next-generation antibiotic tool in industrial and clinical fields.

8.
Nanomaterials (Basel) ; 11(2)2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33498491

RESUMEN

Zinc oxide (ZnO) nano/microparticles (NPs/MPs) have been studied as antibiotics to enhance antimicrobial activity against pathogenic bacteria and viruses with or without antibiotic resistance. They have unique physicochemical characteristics that can affect biological and toxicological responses in microorganisms. Metal ion release, particle adsorption, and reactive oxygen species generation are the main mechanisms underlying their antimicrobial action. In this review, we describe the physicochemical characteristics of ZnO NPs/MPs related to biological and toxicological effects and discuss the recent findings of the antimicrobial activity of ZnO NPs/MPs and their combinations with other materials against pathogenic microorganisms. Current biomedical applications of ZnO NPs/MPs and combinations with other materials are also presented. This review will provide the better understanding of ZnO NPs/MPs as antibiotic alternatives and aid in further development of antibiotic agents for industrial and clinical applications.

9.
Nanomaterials (Basel) ; 10(12)2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33255791

RESUMEN

Subunit vaccines consist of non-genetic material, such as peptides or proteins. They are considered safe because they have fewer side effects; however, they have low immunogenicity when used alone. We aimed to enhance the immune response of peptide-based vaccines by using self-assembled multimeric peptide amphiphiles (PAs). We designed two epitope PAs by conjugating epitope peptides from Enterovirus 71 (EV71) virus particle (VP) 1 and VP3 capsid proteins with different fatty acid chain lengths (VP1PA and VP3PA). These PAs self-assembled into supramolecular structures at a physiological pH, and the resulting structures were characterized using atomic force microscopy. Multi-epitope PAs (m-PAs) consisted of a 1:1 mixture of VP1PA and VP3PA solutions. To evaluate immunogenicity, m-PA constructs were injected with adjuvant subcutaneously into female Balb/c mice. Levels of antigen-specific immunoglobulin G (IgG) and IgG1 in m-PA-injected mice serum samples were analyzed using ELISA and Western blotting. Additionally, cytokine production stimulated by each antigen was measured in splenocytes cultured from immunized mice groups. We found that m-PA showed improved humoral and cellular immune responses compared to the control and peptide groups. The sera from m-PA immunized mice group could neutralize EV71 infection and protect host cells. Thus, self-assembled m-PAs can promote a protective immune response and can be developed as a potential platform technology to produce peptide vaccines against infectious viral diseases.

10.
Pharmaceutics ; 12(8)2020 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-32707862

RESUMEN

Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.

11.
J Nanosci Nanotechnol ; 20(9): 5329-5332, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32331099

RESUMEN

Peptide-based vaccines are relatively safe but have weak immune responses even with an adjuvant. In order to overcome the limitations of peptide-based vaccines, we developed peptide amphiphile (PA)-based nanofibers to enhance the immune responses for preventing enterovirus 71 (EV71) infectious disease (i.e., Hand, Foot, and Mouth Disease). PAs are peptides conjugated with fatty acid alkyl chain and able to self-assemble into various structures including high-aspectratio nanofibers. We designed PAs by coupling EV71 virus particle 1 (VP1) epitope peptides and spacer-crosslinker to the N-terminal of long-chain fatty acids (VP1-PA). PAs then self-assembled into nanofibers at physiological pH (pH 7.4). PA nanofibers were characterized by atomic force microscopy (AFM). For the immunization studies, C57BL/6 mice were injected intraperitoneally (i.p.) with recombinant VP1 with adjuvant (alum), VP1 epitope peptide with or without adjuvant, VP1-PA nanofibers with or without adjuvant, and PBS. To assess the immunogenecity of the VP1-PA nanofibers on serum samples from the immunized mice was analyzed by Western blot for the evaluation of VP1-specific IgG. The PA group showed a higher immune response than the peptide group. We expect that self-assembling VP1-PA based nanofibers as an immune stimulator could enhance immune responses effectively against EV71 infection and overcome the limitations of peptide-based vaccine.


Asunto(s)
Enfermedades Transmisibles , Enterovirus Humano A , Nanofibras , Vacunas Virales , Animales , Anticuerpos Antivirales , Epítopos , Ratones , Ratones Endogámicos C57BL , Péptidos
12.
Pharmaceutics ; 11(11)2019 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-31689932

RESUMEN

Zinc oxide (ZnO) nanoparticles have been studied as metal-based drugs that may be used for biomedical applications due to the fact of their biocompatibility. Their physicochemical properties, which depend on synthesis techniques involving physical, chemical, biological, and microfluidic reactor methods affect biological activity in vitro and in vivo. Advanced tool-based physicochemical characterization is required to identify the biological and toxicological effects of ZnO nanoparticles. These nanoparticles have variable morphologies and can be molded into three-dimensional structures to enhance their performance. Zinc oxide nanoparticles have shown therapeutic activity against cancer, diabetes, microbial infection, and inflammation. They have also shown the potential to aid in wound healing and can be used for imaging tools and sensors. In this review, we discuss the synthesis techniques, physicochemical characteristics, evaluation tools, techniques used to generate three-dimensional structures, and the various biomedical applications of ZnO nanoparticles.

13.
RSC Adv ; 9(67): 39111-39118, 2019 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-35540674

RESUMEN

M13 bacteriophage (phage) nano- and microfibers were fabricated using electrospinning. Using liquid crystalline suspension of the phage, we successfully fabricated nano- and microscale pure phage fibers. Through a near field electrospinning process, we fabricated the desired phage fiber pattern with tunable direction and spacing. In addition, we demonstrated that the resulting phage fibers could be utilized as an electrostatic-stimulus responsive actuator. The near field electrospinning would be a very useful tool to design phage-based chemical sensors, tissue regenerative materials, energy generators, metallic and semiconductor nanowires in the future.

14.
Int J Biol Macromol ; 125: 61-71, 2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-30521919

RESUMEN

Polyethylene glycol (PEG)-decorated doxorubicin (Dox)/carboxymethyl chitosan (CMC)/gold nanoparticles (AuNPs) have been developed for cancer therapy. CMC was used as a reducing and stabilizing agent for the fabrication of AuNPs and Dox was loaded onto AuNPs as a chemotherapeutic agent. Dox-loaded CMC-stabilized AuNPs (Dox/CMC-AuNPs) with a mean diameter of 104.0 nm, zeta potential of -48.32 mV, and drug loading efficiency of 60.14% were prepared. PEG was attached to CMC-AuNPs for enhancing systemic drug exposure and prolonging the circulation in blood stream. Compared with Dox/CMC-AuNPs, Dox-loaded PEGylated CMC-AuNPs (Dox/CMC-AuNPs-PEG) showed a reduced hydrodynamic size (71.2 nm), less negative zeta potential (-12.83 mV), and an enhanced Dox loading efficiency (73.14%). Dox/CMC-AuNPs and Dox/CMC-AuNPs-PEG exhibited sustained and pH-dependent drug release profiles and exhibited antiproliferation effects against the A549 cells. In a bi-directional transport study of Caco-2 cell monolayers, AuNPs reduced the efflux ratio, which indicated that the P-glycoprotein-mediated multidrug resistance (MDR) was overcome. Dox/CMC-AuNPs-PEG resulted in reduced drug clearance (CL) and improved half-life (t1/2), compared with Dox/CMC-AuNPs, in rats after intravenous administration. These results suggest that Dox/CMC-AuNPs-PEG could be a promising nanotherapeutic approach to overcome MDR in cancer and prolong their circulation in the blood stream.


Asunto(s)
Quitosano/análogos & derivados , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Oro , Nanopartículas del Metal , Polietilenglicoles , Animales , Línea Celular Tumoral , Quitosano/química , Cromatografía Liquida , Doxorrubicina/química , Portadores de Fármacos , Liberación de Fármacos , Estabilidad de Medicamentos , Oro/química , Humanos , Masculino , Nanopartículas del Metal/química , Polietilenglicoles/química , Ratas , Espectrometría de Masas en Tándem
15.
J Nanosci Nanotechnol ; 19(2): 687-690, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30360142

RESUMEN

Gold nanoparticles (AuNPs) have been widely used as drug delivery carriers for cancer targeting and therapy. In this study, we developed mitoxantrone (MX)-loaded poly(ethylene glycol)-modified AuNPs complexes (AuNPs-PEG-MX) and evaluated its physicochemical properties compared to AuNPs, free MX, and MX-loaded AuNPs (AuNPs-MX). The results of surface plasmon resonance (SPR) measurement provided corresponded characteristics of free MX and AuNP groups, which determined by electrophoretic light scattering (ELS) method. The hydrodynamic size of AuNPs-PEG-MX was lower than that of AuNPs-MX. Furthermore, loading efficiency of AuNPs-PEG-MX was 1.9-fold increased than AuNPs-MX. In addition, AuNPs-PEG-MX showed similar cytotoxicity compared to AuNPs-MX group in HeLa cells with enhanced drug release. Conclusively, AuNPs-PEG-MX could be applied for in vivo cancer therapy via passive targeting based on the enhanced permeability and retention effect after intravenous injection.


Asunto(s)
Nanopartículas del Metal , Neoplasias , Oro , Células HeLa , Humanos , Mitoxantrona , Neoplasias/tratamiento farmacológico , Polietilenglicoles
16.
ACS Nano ; 12(8): 8138-8144, 2018 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-30071165

RESUMEN

Piezoelectric materials are excellent generators of clean energy, as they can harvest the ubiquitous vibrational and mechanical forces. We developed large-scale unidirectionally polarized, aligned diphenylalanine (FF) nanotubes and fabricated peptide-based piezoelectric energy harvesters. We first used the meniscus-driven self-assembly process to fabricate horizontally aligned FF nanotubes. The FF nanotubes exhibit piezoelectric properties as well as unidirectional polarization. In addition, the asymmetric shapes of the self-assembled FF nanotubes enable them to effectively translate external axial forces into shear deformation to generate electrical energy. The fabricated peptide-based piezoelectric energy harvesters can generate voltage, current, and power of up to 2.8 V, 37.4 nA, and 8.2 nW, respectively, with 42 N of force, and can power multiple liquid-crystal display panels. These peptide-based energy-harvesting materials will provide a compatible energy source for biomedical applications in the future.


Asunto(s)
Fuentes Generadoras de Energía , Nanotubos/química , Péptidos/química , Fenilalanina/análogos & derivados , Dipéptidos , Cristales Líquidos/química , Estructura Molecular , Tamaño de la Partícula , Fenilalanina/química , Propiedades de Superficie
17.
Methods Mol Biol ; 1776: 487-502, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29869262

RESUMEN

M13 bacteriophages have several qualities that make them attractive candidates as building blocks for tissue regenerating scaffold materials. Through genetic engineering, a high density of functional peptides and proteins can be simultaneously displayed on the M13 bacteriophage's outer coat proteins. The resulting phage can self-assemble into nanofibrous network structures and can guide the tissue morphogenesis through proliferation, differentiation and apoptosis. In this manuscript, we will describe methods to develop major coat-engineered M13 phages as a basic building block and aligned tissue-like matrices to develop regenerative nanomaterials.


Asunto(s)
Bacteriófago M13/genética , Ingeniería Genética/métodos , Ingeniería de Tejidos/métodos , Bacteriófago M13/química , Diferenciación Celular/genética , Proliferación Celular/genética , Regeneración/genética , Andamios del Tejido
18.
Sci Rep ; 8(1): 5216, 2018 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-29581559

RESUMEN

Calcium phosphate cements (CPCs) are synthetic bioactive cements widely used as hard tissue substitutes. Critical limitations of use include their poor mechanical properties and poor anti-washout behaviour. To address those limitations, we combined CPC with genetically engineered elastin-like polypeptides (ELPs). We investigated the effect of the ELPs on the physical properties and biocompatibility of CPC by testing ELP/CPC composites with various liquid/powder ratios. Our results show that the addition of ELPs improved the mechanical properties of the CPC, including the microhardness, compressive strength, and washout resistance. The biocompatibility of ELP/CPC composites was also comparable to that of the CPC alone. However, supplementing CPC with ELPs functionalized with octaglutamate as a hydroxyapatite binding peptide increased the setting time of the cement. With further design and modification of our biomolecules and composites, our research will lead to products with diverse applications in biology and medicine.


Asunto(s)
Cementos para Huesos/química , Fosfatos de Calcio/química , Elastina/química , Péptidos/química , Materiales Biocompatibles/química , Materiales Biocompatibles/uso terapéutico , Cementos para Huesos/uso terapéutico , Fosfatos de Calcio/uso terapéutico , Cementos Dentales/química , Cementos Dentales/uso terapéutico , Elastina/uso terapéutico , Dureza , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Péptidos/uso terapéutico , Fenómenos Físicos , Difracción de Rayos X
19.
Int J Nanomedicine ; 12: 8057-8070, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29138562

RESUMEN

Metal oxide (MO) nanoparticles have been studied as nano-antibiotics due to their antimicrobial activities even in antibiotic-resistant microorganisms. We hypothesized that a hybrid system of dual UV irradiation and MO nanoparticles would have enhanced antimicrobial activities compared with UV or MO nanoparticles alone. In this study, nanoparticles of ZnO, ZnTiO3, MgO, and CuO were selected as model nanoparticles. A dual UV collimated beam device of UV-A and UV-C was developed depending upon the lamp divided by coating. Physicochemical properties of MO nanoparticles were determined using powder X-ray diffractometry (PXRD), Brunauer-Emmett-Teller analysis, and field emission-scanning electron microscopy with energy-dispersive X-ray spectroscopy. Atomic force microscopy with an electrostatic force microscopy mode was used to confirm the surface topology and electrostatic characteristics after dual UV irradiation. For antimicrobial activity test, MO nanoparticles under dual UV irradiation were applied to Escherichia coli and M13 bacteriophage (phage). The UV-A and UV-C showed differential intensities in the coated and uncoated areas (UV-A, coated = uncoated; UV-C, coated ≪ uncoated). MO nanoparticles showed sharp peaks in PXRD patterns, matched to pure materials. Their primary particle sizes were less than 100 nm with irregular shapes, which had an 8.6~25.6 m2/g of specific surface area with mesopores of 22~262 nm. The electrostatic properties of MO nanoparticles were modulated after UV irradiation. ZnO, MgO, and CuO nanoparticles, except ZnTiO3 nanoparticles, showed antibacterial effects on E. coli. Antimicrobial effects on E. coli and phages were also enhanced after cyclic exposure of dual UV and MO nanoparticle treatment using the uncoated area, except ZnO nanoparticles. Our results demonstrate that dual UV-MO nanoparticle hybrid system has a potential for disinfection. We anticipate that it can be developed as a next-generation disinfection system in pharmaceutical industries and water purification systems.


Asunto(s)
Antiinfecciosos/farmacología , Bacteriófago M13/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/efectos de la radiación , Nanopartículas del Metal/química , Antiinfecciosos/química , Bacteriófago M13/efectos de la radiación , Nanopartículas del Metal/administración & dosificación , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Espectrometría por Rayos X , Electricidad Estática , Rayos Ultravioleta , Difracción de Rayos X , Óxido de Zinc/química , Óxido de Zinc/farmacología
20.
ACS Appl Mater Interfaces ; 9(38): 32965-32976, 2017 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-28872295

RESUMEN

We report a virus-incorporated biological template (biotemplate) on electrode surfaces and its use in electrochemical nucleation of metal nanocomposites as an electrocatalytic material for energy applications. The biotemplate was developed with M13 virus (M13) incorporated in a silicate sol-gel matrix as a scaffold to nucleate Au-Pt alloy nanostructures by electrodeposition, together with reduced graphene oxide (rGO). The phage when engineered with Y3E peptides could nucleate Au-Pt alloy nanostructures, which ensured adequate packing density, simultaneous stabilization of rGO, and a significantly increased electrochemically active surface area. Investigation of the electrocatalytic activity of the resulting sol-gel composite catalyst toward methanol oxidation in an alkaline medium showed that this catalyst had mass activity greater than that of the biotemplate containing wild-type M13 and that of monometallic Pt and other Au-Pt nanostructures with different compositions and supports. M13 in the nanocomposite materials provided a close contact between the Au-Pt alloy nanostructures and rGO. In addition, it facilitated the availability of an OH--rich environment to the catalyst. As a result, efficient electron transfer and a synergistic catalytic effect of the Au and Pt in the alloy nanostructures toward methanol oxidation were observed. Our nanocomposite synthesis on the novel biotemplate and its application might be useful for developing novel clean and green energy-generating and energy-storage materials.

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