Spatial control of membrane receptor function using ligand nanocalipers

Shaw, Alan; Lundin, Vanessa; Petrova, Ekaterina; Fördős, Ferenc; Benson, Erik; Al-Amin, Rasel A.; Herland, Anna; Blokzijl, Andries; Högberg, Björn; Teixeira, Ana I.

doi:10.1038/nmeth.3025

Cited by 235 publications

(274 citation statements)

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“…Essentially, they noticed that the delivery of siRNAs strongly depends on the density and the spatial orientation of the cancer-targeting ligands of the nanoparticle. Similarly, it has been observed that the membrane receptor-mediated signaling in cancer cells can be regulated by adjusting the spatial orientation of the membrane-binding ligands with DNA origami "nanocalipers" [38]. These observations elegantly show the potential of DNA-based delivery systems, since the vehicle can be easily programmed and functionalized in a user-defined way.…”

Section: Towards Dna-based Drug Delivery Vehicles and Advanced Therapmentioning

confidence: 86%

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

Linko

Ora

Kostiainen

2015

Trends in Biotechnology

228

166

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Emerging DNA nanotechnologyThe field of structural DNA nanotechnology started around 30 years ago when Ned Seeman performed pioneering research with DNA junctions and lattices [1]. To date, a cornucopia of different DNA nanostructures and shapes based on WatsonCrick basepairing [2] have been designed and demonstrated, and the whole research area has enjoyed a rapid progress especially during the past decade [3]. The key player in the fast development of DNA nanotechnology has been the invention of DNA origami in 2006 [4]. The DNA origami method is based on folding a long single-stranded "DNA scaffold strand" into a customized shape with a set of short synthetic staple strands. The robustness of the technique has made it widely accessible.Since then, the method has been generalized to 3D-fabrication [5][6][7][8][9][10], and it enables shapes with custom curvatures, twists and bends [11,12]. Very recently, techniques for modular scaffold-free fabrication [13,14], 3D meshing and wireframe-based approaches [15][16][17], as well as shape-complementarity-based construction [18] of DNA objects have been introduced. In addition, powerful computational tools for designing and analyzing DNA nanostructures have been developed [19][20][21], which appreciably help researchers to create their own DNA nanoarchitectures for any conceivable application. Table 1 lists and 2 describes the novel design strategies that can be used for fabricating diverse DNA origami nanostructures and other complex DNA-based shapes for various nanotechnological purposes.The platonic DNA nanostructures and DNA origamis are by all means remarkably impressive examples of precise engineering and constructing at the nanoscale. However, the attractiveness of the origami method lies in the fact that one can add any desired functionality to the tailored DNA shapes by assembling other biomolecules and molecular components to them with nanometer precision. Importantly, DNA is inherently biocompatible, and its stability can be further tuned by the optional functionalization [20,[22][23][24]. Aforementioned superior features can be eventually exploited in designing artificial DNA-based biomachinery, such as nucleic acid devices [25] and protein-DNA hybrid structures [26] for nanomedicine and biosensing. In this focused review, we discuss the recent progress of the nanomedical applications of self-assembled DNA systems; especially the drug delivery vehicles and nanomachines based on the DNA origami technique. Towards DNA-based drug delivery vehicles and advanced therapeuticsThe tremendous self-assembly properties of DNA can be exploited in creating various programmable shapes and larger assemblies for cellular delivery for e.g. cancer and enzyme replacement therapy. The very first DNA origami nano-objects proposed to work as molecular containers for drug delivery applications were single-layer origamis, which were further assembled into 3D shapes -a tetrahedron [5] or hollow cubes [6,7] (Fig. 1A). Since then, cellular uptake for various DNA structures (based o...

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Section: Towards Dna-based Drug Delivery Vehicles and Advanced Therapmentioning

confidence: 86%

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

Linko

Ora

Kostiainen

2015

Trends in Biotechnology

228

166

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“…Hence, the ectodomain of ephrin-B2, normally an integral membrane protein ligand, was conjugated to a soluble biopolymer (hyaluronic acid) to yield multivalent nanoscale conjugates that induced signaling in neural stem cells and promoted their neuronal differentiation in vitro and in vivo. In another nanotechnological twist on the same topic, Shaw et al (12) designed DNA origami nanostructures modified with ligands at well-defined positions and showed that the nanoscale spacing of ephrin-A5 controls membrane receptor activation in breast cancer cells and regulates their invasive behavior. Thus, it is clear that cells are not unacquainted with "nano"; in fact, cells in our body are capable of 'sensing' and responding to nanostructured surfaces.…”

Section: The Right Size In Nanotoxicologymentioning

confidence: 99%

Keeping it small: towards a molecular definition of nanotoxicology

Gallud

Fadeel

2015

European Journal of Nanomedicine

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Abstract:In this essay, we offer the opinion that engineered nanomaterials are, by definition, materials that can interact with biological systems at the nanoscale, and that this very fact underlies both the promise and the peril of this multifaceted class of materials. Furthermore, nanomaterials are cloaked in host-derived proteins, lipids, or other biomolecules as they enter into a living organism and this so-called bio-corona may impact on subsequent interactions with biological structures. We will explore some examples of nanoscale effects of engineered nanomaterials, and discuss how such interactions may underpin toxicity, and, conversely, how nanoscale interactions may be harnessed for clinical applications, including the use of nanoparticles as drugs per se.Keywords: biological mimicry; cellular nanomachineries; engineered nanomaterials; molecular dynamics simulations; nanomedicine; nanotopographies; nanotoxicology. Life is a nanoscale phenomenonIn their seminal paper published one decade ago, Donaldson et al. (1) proposed that a new subcategory of toxicology -namely nanotoxicology -be defined to specifically address "the special problems likely to be caused by nanoparticles", and the authors suggested that nanotoxicology be considered "a new frontier in particle toxicology". However, one may argue, instead, that nanotoxicology represents a departure from the traditional toxicology of fine and ultrafine particles and fibers. In fact, nanotoxicology may be understood in light of "the interference of engineered nanomaterials with the functions of cellular and extracellular nanomachineries" (2). This view places emphasis on the fact that life (biology) is "a nanoscale phenomenon" (3). Indeed, living organisms are host to a range of dedicated intra-and extracellular nanoscale machines (4) and this, therefore, suggests that specific, size-dependent toxicities may ensue as a result of exposure to engineered nanomaterials. This does not, however, mean that all nanomaterials are inherently toxic (5), or that a nanospecific effect is necessarily detrimental to the host; in fact, the controlled manipulation of biological systems at the nanoscale may very well open up for novel therapeutic approaches. In this essay, we will explore both sides of the coin. The right size in nanotoxicologyIn his review on "the 'right' size in nanobiotechnology", Whitesides argued that "small" -both nano and micromust be a part of the future of biotechnology; which size is most important depends on what question one is asking (6). Surprisingly, in the field of nanotoxicology, the question of size, and more specifically, how one should define a nanomaterial (indeed, whether or not one should define nanomaterials in the first place) remains a matter of debate. Hence, while some have argued that we should not define nanomaterials, or to be more precise, that a 'one-size-fitsall' definition of nanomaterials will fail to capture what is important for addressing risk (7), others have stated that a definition of nanomaterials for regulatory ...

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“…[12] Fluorophores have been added to study energy transfer [13] and to create nanoscale barcodes. [14] DNAo rigami structures have also been used to control the shape of metal particles [15] and graphene sheets.…”

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confidence: 99%

Computer‐Aided Production of Scaffolded DNA Nanostructures from Flat Sheet Meshes

et al. 2016

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The use of DNAa sananoscale construction material has been ar apidly developing field since the 1980s, in particular since the introduction of scaffolded DNAorigami in 2006. Although software is available for DNAo rigami design, the user is generally limited to architectures where finding the scaffold path through the object is trivial. Herein, we demonstrate the automated conversion of arbitrary twodimensional sheets in the form of digital meshes into scaffolded DNAn anostructures.W ei nvestigate the properties of DNA meshes based on three different internal frameworks in standardf olding buffer and physiological salt buffers.W e then employ the triangulated internal framework and produce four 2D structures with complex outlines and internal features. We demonstrate that this highly automated technique is capable of producing complex DNAn anostructures that fold with high yield to their programmed configurations,c overing around 70 %more surface area than classic origami flat sheets.Since its introduction in the 1980s, [1] DNAn anotechnology has been arapidly growing and diversifying field. This growth has accelerated since the introduction of scaffolded DNA origami in 2006.[2] In aDNA origami structure,along strand, called the scaffold, traverses the entire structure pairing with hundreds of oligonucleotides,c alled staple strands,t hat hold the structure together.The structures are often based around as quare or honeycomb lattice [3] where finding the scaffold path and designing staples is relatively easy,e specially when using software like caDNAno.[4] DNAn anostructures based on small polyhedra have been demonstrated with both scaffolded [5] and non-scaffolded [6] designs.S caffolded DNA nanostructures based on meshwork designs have also been demonstrated with crossing four-arm junctions, [7] with others containing meshes with two DNAd ouble helices per edge. [8] However,n og eneral strategy for producing arbitrary wireframe 2D structures has been demonstrated.Am ajor branch of research has been the addition of functional elements to DNAn anostructures to give them novel properties.C arbon nanotubes and metal nanoparticles have been added for electronic [9] and plasmonic [10] applications.P roteins have been added for templating enzymatic reactions [11] or cell signaling studies. [12] Fluorophores have been added to study energy transfer [13] and to create nanoscale barcodes.[14] DNAo rigami structures have also been used to control the shape of metal particles [15] and graphene sheets.[16] Demonstrations of drug loading [17] and lipid encapsulation [18] indicate that DNAn anostructures could serve as drug delivery tools.M any applications rely on single layer DNAo bjects as they offer the largest 2D canvas for functionalization and are rigid when immobilized on surfaces.Building on Rothemunds method [2] fors caffolded DNA nanostructures,w er ecently developed am ethod for automatically generating wireframe structures from polyhedral meshes. [19] This method relies on an algorithm for finding an E...

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Spatial control of membrane receptor function using ligand nanocalipers

Cited by 235 publications

References 36 publications

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

Keeping it small: towards a molecular definition of nanotoxicology

Computer‐Aided Production of Scaffolded DNA Nanostructures from Flat Sheet Meshes

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