DNA molecules can be assembled into custom predesigned shapes via hybridization of sequence-complementary domains. The folded structures have high spatial addressability and a tremendous potential to ...serve as platforms and active components in a plethora of bionanotechnological applications. DNA is a truly programmable material, and its nanoscale engineering thus opens up numerous attractive possibilities to develop novel methods for therapeutics. The tailored molecular devices could be used in targeting cells and triggering the cellular actions in the biological environment. In this review we focus on the DNA-based assemblies – primarily DNA origami nanostructures – that could perform complex tasks in cells and serve as smart drug-delivery vehicles in, for example, cancer therapy, prodrug medication, and enzyme replacement therapy.
Abstract
Doxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and ...therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.
Biorenewable polymers have emerged as an attractive alternative to conventional metallic and organic materials for a variety of different applications. This is mainly because of their ...biocompatibility, biodegradability and low cost of production. Lignocellulosic biomass is the most promising renewable carbon-containing source on Earth. Depending on the origin and species of the biomass, lignin consists of 20-35% of the lignocellulosic biomass. After it has been extracted, lignin can be modified through diverse chemical reactions. There are different categories of chemical modifications, such as lignin depolymerization or fragmentation, modification by synthesizing new chemically active sites, chemical modification of the hydroxyl groups, and the production of lignin graftcopolymers. Lignin can be used for different industrial and biomedical applications, including biofuels, chemicals and polymers, and the development of nanomaterials for drug delivery but these uses depend on the source, chemical modifications and physicochemical properties. We provide an overview on the composition and properties, extraction methods and chemical modifications of lignin in this review. Furthermore, we describe different preparation methods for lignin-based nanomaterials with antioxidant UV-absorbing and antimicrobial properties that can be used as reinforcing agents in nanocomposites, in drug delivery and gene delivery vehicles for biomedical applications.
The research field entitled structural DNA nanotechnology emerged in the beginning of the 1980s as the first immobile synthetic nucleic acid junctions were postulated and demonstrated. Since then, ...the field has taken huge leaps toward advanced applications, especially during the past decade. This Progress Report summarizes how the controllable, custom, and accurate nanostructures have recently evolved together with powerful design and simulation software. Simultaneously they have provided a significant expansion of the shape space of the nanostructures. Today, researchers can select the most suitable fabrication methods, and design paradigms and software from a variety of options when creating unique DNA nanoobjects and shapes for a plethora of implementations in materials science, optics, plasmonics, molecular patterning, and nanomedicine.
DNA nanotechnology flourishes. Here, the recent progress of structural DNA nanotechnology is reviewed by presenting versatile design strategies and computer‐aided software for design and simulation of nanoshapes. Evolution in the field is projected to lead to the development of novel biomaterials and advanced applications.
DNA nanotechnology enables straightforward fabrication of user-defined and nanometer-precise templates for a cornucopia of different uses. To date, most of these DNA assemblies have been static, but ...dynamic structures are increasingly coming into view. The programmability of DNA not only allows for encoding of the DNA object shape but also it may be equally used in defining the mechanism of action and the type of stimuli-responsiveness of the dynamic structures. However, these “robotic” features of DNA nanostructures are usually demonstrated for only small, discrete, and device-like objects rather than for collectively behaving higher-order systems. Here, we show how a large-scale, two-dimensional (2D) and pH-responsive DNA origami-based lattice can be assembled into two different configurations (“open” and “closed” states) on a mica substrate and further switched from one to the other distinct state upon a pH change of the surrounding solution. The control over these two configurations is achieved by equipping the arms of the lattice-forming DNA origami units with “pH-latches” that form Hoogsteen-type triplexes at low pH. In short, we demonstrate how the electrostatic control over the adhesion and mobility of the DNA origami units on the surface can be used both in the large lattice formation (with the help of directed polymerization) and in the conformational switching of the whole lattice. To further emphasize the feasibility of the method, we also demonstrate the formation of pH-responsive 2D gold nanoparticle lattices. We believe this work can bridge the nanometer-precise DNA origami templates and higher-order large-scale systems with the stimuli-induced dynamicity.
DNA origami structures have great potential as functional platforms in various biomedical applications. Many applications, however, are incompatible with the high Mg2+ concentrations commonly ...believed to be a prerequisite for maintaining DNA origami integrity. Herein, we investigate DNA origami stability in low‐Mg2+ buffers. DNA origami stability is found to crucially depend on the availability of residual Mg2+ ions for screening electrostatic repulsion. The presence of EDTA and phosphate ions may thus facilitate DNA origami denaturation by displacing Mg2+ ions from the DNA backbone and reducing the strength of the Mg2+–DNA interaction, respectively. Most remarkably, these buffer dependencies are affected by DNA origami superstructure. However, by rationally selecting buffer components and considering superstructure‐dependent effects, the structural integrity of a given DNA origami nanostructure can be maintained in conventional buffers even at Mg2+ concentrations in the low‐micromolar range.
The stability of DNA origami nanostructures in various Tris and phosphate‐based buffers was evaluated at residual Mg2+ concentrations in the low‐micromolar range. DNA origami stability was found to be crucially affected by the presence of EDTA and phosphate ions that may displace bound Mg2+ ions from the DNA backbone and reduce the strength of the Mg2+–DNA interaction, respectively. These effects furthermore depend on DNA origami superstructure.
In this communication, we present a nanoscale reactor assembled from tuneable and spatially addressable tubular DNA origami units. We can controllably combine separate origami units equipped with ...glucose oxidase (GOx) and horseradish peroxidase (HRP), and demonstrate efficient GOx/HRP enzyme cascade reaction inside the tube. The reactor could be utilized as a nanoscale diagnostic tool, and modularity of the proposed system would further enable more complex reactions.
DNA nanotechnology provides a toolbox for creating custom and precise nanostructures with nanometer-level accuracy. These nano-objects are often static by nature and serve as versatile templates for ...assembling various molecular components in a user-defined way. In addition to the static structures, the intrinsic programmability of DNA nanostructures allows the design of dynamic devices that can perform predefined tasks when triggered with external stimuli, such as drug delivery vehicles whose cargo display or release can be triggered with a specified physical or chemical cue in the biological environment. Here, we present a DNA origami nanocapsule that can be loaded with cargo and reversibly opened and closed by changing the pH of the surrounding solution. Moreover, the threshold pH value for opening/closing can be rationally designed. We characterize the reversible switching and a rapid opening of “pH-latch”-equipped nanocapsules using Förster resonance energy transfer. Furthermore, we demonstrate the full cycle of capsule loading, encapsulation, and displaying the payload using metal nanoparticles and functional enzymes as cargo mimics at physiologically relevant ion concentrations.
Binary nanoparticle superlattices are periodic nanostructures with lattice constants much shorter than the wavelength of light and could be used to prepare multifunctional metamaterials. Such ...superlattices are typically made from synthetic nanoparticles, and although biohybrid structures have been developed, incorporating biological building blocks into binary nanoparticle superlattices remains challenging. Protein-based nanocages provide a complex yet monodisperse and geometrically well-defined hollow cage that can be used to encapsulate different materials. Such protein cages have been used to program the self-assembly of encapsulated materials to form free-standing crystals and superlattices at interfaces or in solution. Here, we show that electrostatically patchy protein cages--cowpea chlorotic mottle virus and ferritin cages--can be used to direct the self-assembly of three-dimensional binary superlattices. The negatively charged cages can encapsulate RNA or superparamagnetic iron oxide nanoparticles, and the superlattices are formed through tunable electrostatic interactions with positively charged gold nanoparticles. Gold nanoparticles and viruses form an AB(8)(fcc) crystal structure that is not isostructural with any known atomic or molecular crystal structure and has previously been observed only with large colloidal polymer particles. Gold nanoparticles and empty or nanoparticle-loaded ferritin cages form an interpenetrating simple cubic AB structure (isostructural with CsCl). We also show that these magnetic assemblies provide contrast enhancement in magnetic resonance imaging.
A simple process for lignin nanoparticle preparation Lievonen, Miikka; Valle-Delgado, Juan Jose; Mattinen, Maija-Liisa ...
Green chemistry : an international journal and green chemistry resource : GC,
01/2016, Letnik:
18, Številka:
5
Journal Article
Recenzirano
Odprti dostop
A lack of renewable resources and their inefficient use is a major challenge facing the society. Lignin is a natural biopolymer obtained mainly as a by-product from the pulp- and paper-making ...industries, and is primarily burned to produce energy. However, interest for using lignin in more advanced applications has increased rapidly. In particular, lignin based nanoparticles could find potential use in functional surface coatings, nanoglue, drug delivery, and microfluidic devices. In this work, a straightforward method to produce lignin nanoparticles from waste lignin obtained from kraft pulping is introduced. Spherical lignin nanoparticles were obtained by dissolving softwood kraft lignin in tetrahydrofuran (THF) and subsequently introducing water into the system through dialysis. No chemical modification of lignin was needed. Water acts as a non-solvent reducing lignin's degrees of freedom causing the segregation of hydrophobic regions to compartments within the forming nanoparticles. The final size of the nanoparticles depended on the pre-dialysis concentration of dissolved lignin. The stability of the nanoparticle dispersion as a function of time, salt concentration and pH was studied. In pure water and at room temperature the lignin nanoparticle dispersion was stable for over two months, but a very low pH or high salt concentration induced aggregation. It was further demonstrated that the surface charge of the particles could be reversed and stable cationic lignin nanoparticles were produced by adsorption of poly(diallyldimethylammonium chloride) (PDADMAC).
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