RESUMEN
Since its discovery in 2006, the DNA origami technique has revolutionized bottom-up nanofabrication. This technique is simple yet versatile and enables the fabrication of nanostructures of almost arbitrary shapes. Furthermore, due to their intrinsic addressability, DNA origami structures can serve as templates for the arrangement of various nanoscale components (small molecules, proteins, nanoparticles, etc.) with controlled stoichiometry and nanometer-scale precision, which is often beyond the reach of other nanofabrication techniques. Despite the multiple benefits of the DNA origami technique, its applicability is often restricted by the limited stability in application-specific conditions. This Review provides an overview of the strategies that have been developed to improve the stability of DNA-origami-based assemblies for potential biomedical, nanofabrication, and other applications.
Asunto(s)
Nanopartículas , Nanoestructuras , ADN/química , Nanoestructuras/química , Conformación de Ácido Nucleico , Nanotecnología/métodosRESUMEN
We report the modular formulation of ciprofloxacin-based pure theranostic nanodrugs that display enhanced antibacterial activities, as well as aggregation-induced emission (AIE) enhancement that was successfully used to image bacteria. The drug derivatives, consisting of ciprofloxacin, a perfluoroaryl ring, and a phenyl ring linked by an amidine bond, were efficiently synthesized by a straightforward protocol from a perfluoroaryl azide, ciprofloxacin, and an aldehyde in acetone at room temperature. These compounds are propeller-shaped, and upon precipitation into water, readily assembled into stable nanoaggregates that transformed ciprofloxacin derivatives into AIE-active luminogens. The nanoaggregates displayed increased luminescence and were successfully used to image bacteria. In addition, these nanodrugs showed enhanced antibacterial activities, lowering the minimum inhibitory concentration (MIC) by more than one order of magnitude against both sensitive and resistant Escherichia coli The study represents a strategy in the design and development of pure theranostic nanodrugs for combating drug-resistant bacterial infections.
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Ciprofloxacina/análogos & derivados , Ciprofloxacina/síntesis química , Ciprofloxacina/farmacología , Antibacterianos/síntesis química , Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Diseño de Fármacos , Farmacorresistencia Bacteriana , Fluoroquinolonas/química , Luminiscencia , Pruebas de Sensibilidad Microbiana , Nanomedicina TeranósticaRESUMEN
The ability of proteins to form hierarchical structures through self-assembly provides an opportunity to synthesize and organize nanoparticles. Ordered nanoparticle assemblies are a subject of widespread interest due to the potential to harness their emergent functions. In this work, the toroidal-shaped form of the protein peroxiredoxin, which has a pore size of 7 nm, was used to organize iron oxyhydroxide nanoparticles. Iron in the form of Fe2+ was sequestered into the central cavity of the toroid ring using metal-binding sites engineered there and then hydrolyzed to form iron oxyhydroxide particles bound into the protein pore. By precise manipulation of the pH, the mineralized toroids were organized into stacks confining one-dimensional nanoparticle assemblies. We report the formation and the procedures leading to the formation of such nanostructures and their characterization by chromatography and microscopy. Electrostatic force microscopy clearly revealed the formation of iron-containing nanorods as a result of the self-assembly of the iron-loaded protein. This research bodes well for the use of peroxiredoxin as a template with which to form nanowires and structures for electronic and magnetic applications.
Asunto(s)
Nanopartículas/química , Peroxirredoxinas/química , Compuestos Férricos/química , Concentración de Iones de Hidrógeno , Hierro/química , Nanotecnología , Tamaño de la Partícula , Porosidad , Unión Proteica , Multimerización de Proteína , Electricidad EstáticaRESUMEN
Hydrogels are excellent soft materials to interface with biological systems. Precise control and tunability of dissipative properties of gels are particularly interesting in tissue engineering applications. In this work, we produced hydrogels with tunable dissipative properties by photopolymerizing a second polymer within a preformed cross-linked hydrogel network of poly(acrylamide). We explored second networks made with different structures and capacity to hydrogen bond with the first network, namely linear poly(acrylic acid) and branched poly(tannic acid). Gels incorporating a second network made with poly(tannic acid) exhibited excellent stiffness (0.35 ± 0.035 MPa) and toughness (1.64 ± 0.26 MJ m-3) compared to the poly(acrylic acid) counterparts. We also demonstrate a strategy to fabricate hydrogels where the dissipation (loss modulus) can be tuned independently from the elasticity (storage modulus) suitable for cell culture applications. We anticipate that this modular design approach for producing hydrogels will have applications in tailored substrates for cell culture studies and in load bearing tissue engineering applications.
RESUMEN
Atomic force microscopy (AFM) enables imaging of surface-deposited proteins and protein structures under physiological conditions, which is a benefit compared to ultra-high vacuum techniques such as electron microscopy. AFM also has the potential to provide more information from the phase in tapping mode or from functional AFM modes. The sample preparation, probe selection, and imaging conditions are crucial for successful imaging of proteins. Here we give a detailed account of the steps toward imaging of soft samples in both air and liquid along with the basic theory underpinning these details.
Asunto(s)
Microscopía de Fuerza Atómica/métodos , Proteínas/química , Proteínas/metabolismoRESUMEN
The fluorescence properties of AIE-active N-amidinated fluoroquinolones, efficiently obtained by a perfluoroaryl azide-aldehyde-amine reaction, have been studied. The fluorophores were discovered to elicit a highly sensitive fluorescence quenching response towards guest molecules with hydrogen-bond-donating ability. This effect was evaluated in a range of protic/aprotic solvents with different H-bonding capabilities, and also in aqueous media. The influence of acid/base was furthermore addressed. The hydrogen-bonding interactions were studied by IR, NMR, UV/Vis and time-resolved fluorescence decay, revealing their roles in quenching of the fluorescence emission. Due to the pronounced quenching property of water, the N-amidinated fluoroquinolones could be utilized as fluorescent probes for quantifying trace amount of water in organic solvents.
RESUMEN
Gout is an abnormality in the body resulting in the accumulation of uric acid mainly in joints. Dissolution of uric acid crystals into soluble allantoin by the enzyme uricase might provide a better alternative for the treatment of gout. This work aims to investigate the feasibility of a transdermal patch loaded with uricase for better patient compliance. Mesoporous silica (SBA-15) was chosen as the matrix for immobilisation of uricase. Highly oriented mesoporous SBA-15 was synthesized, characterized and uricase was physisorbed in the mesoporous material. The percentage adsorption and release of enzyme in borate buffer was monitored. The release followed linear kinetics and greater than 80% enzyme activity was retained indicating the potential of this system as an effective enzyme immobilization matrix. The enzyme permeability was studied with Wistar rat skin and human cadaver skin. It was found that in case of untreated rat skin 10% of enzyme permeated through skin in 100 h. The permeation increased by adding permeation enhancer (combination of oleic acid in propylene glycol (OA in PG)). The permeation enhancement was studied under two concentrations of OA in PG (1%, 5%) in both rat and human cadaver skin and it was found that 1% OA in PG showed better result in rat skin and 5% OA in PG showed good results in human cadaver skin.