Modular and Chemically Responsive Oligonucleotide “Bonds” in Nanoparticle Superlattices

Barnaby, Stacey N.; Thaner, Ryan V.; Ross, Michael B.; Brown, Keith A.; Schatz, George C.; Mirkin, Chad A.

doi:10.1021/jacs.5b07908

Cited by 25 publications

(37 citation statements)

References 51 publications

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“…Since results from gold-based SNAs indicated that degradation of surface-displayed RNA by serum nucleases can occur rapidly in certain sequence contexts, 22,39,40 we also synthesized 2 ′ F-RPA-NPs that incorporate 2′-fluoropyrimi-dines within the RNA sequence. This sugar modification has proven useful in mediating nuclease resistance and reducing immunogenicity while maintaining efficacy of siRNAs.…”

Section: ■ Resultsmentioning

confidence: 99%

Self-Transfecting Micellar RNA: Modulating Nanoparticle Cell Interactions via High Density Display of Small Molecule Ligands on Micelle Coronas

Roloff¹,

Nelles²,

Thompson³

et al. 2017

Bioconjugate Chem.

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The intracellular delivery of synthetic nucleic acids represents a major challenge in biotechnology and in biomedicine. Methods to deliver short, double-stranded RNA to living cells are of particular interest because of the potential to engage the RNA interference machinery and to regulate mRNA expression. In this work, we describe novel RNA-polymer amphiphiles that assemble into spherical micellar nanoparticles with diameters of ca. 15–30 nm and efficiently enter live cells without transfection reagents. Each micelle consists of approximately 100 RNA strands forming a densely packed corona around a polymeric core. Importantly, the surface-displayed RNA remains accessible for hybridization with complementary RNA. Chemical modification of the termini of hybridized RNA strands enabled the display of small organic moieties on the outer surface of the micelle corona. We found that some of these modifications can have a tremendous impact on cellular internalization efficiencies. The display of hydrophobic dabcyl or stilbene units dramatically increased cell uptake, whereas hydrophilic neutral hydroxy or anionic phosphate residues were ineffective. Interestingly, neither of these modifications mediated noticeable uptake of free RNA oligonucleotides. We infer that their high density display on micellar nanoparticle surfaces is key for the observed effect; achieved with local effective surface concentrations in the millimolar range. We speculate that weak interactions with cell surface receptors that are amplified by the multivalent presentation of such modifications may be responsible. The installation of small molecule ligands on nanomaterial surfaces via hybridization of chemically modified oligonucleotides offers a simple and straightforward way to modulate cellular uptake of nanoparticles. Biological functionality of micellar RNA was demonstrated through the sequence-specific regulation of mRNA expression in HeLa cells.

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Section: ■ Resultsmentioning

confidence: 99%

Self-Transfecting Micellar RNA: Modulating Nanoparticle Cell Interactions via High Density Display of Small Molecule Ligands on Micelle Coronas

Roloff¹,

Nelles²,

Thompson³

et al. 2017

Bioconjugate Chem.

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“…applications. For colloidal crystals in general, notable applications include photonics 4,5 , sensing 6,7 , and catalysis 8,9 . By controlling the relative sizes of colloidal particles in binary systems and the nature of their interactions, a myriad of structures have been produced experimentally from self-assembly: CsCl, NaCl, CuAu, NaTl, AlB 2 , MgZn 2 , Cr 3 Si, Cu 3 Au, Cs 6 C 60 , and others 2,3,[10][11][12][13][14][15] .…”

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confidence: 99%

Assembly of three-dimensional binary superlattices from multi-flavored particles

et al. 2018

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Binary superlattices constructed from nano- or micron-sized colloidal particles have a wide variety of applications, including the design of advanced materials. Self-assembly of such crystals from their constituent colloids can be achieved in practice by, among other means, the functionalization of colloid surfaces with single-stranded DNA sequences. However, when driven by DNA, this assembly is traditionally premised on the pairwise interaction between a single DNA sequence and its complement, and often relies on particle size asymmetry to entropically control the crystalline arrangement of its constituents. The recently proposed "multi-flavoring" motif for DNA functionalization, wherein multiple distinct strands of DNA are grafted in different ratios to different colloids, can be used to experimentally realize a binary mixture in which all pairwise interactions are independently controllable. In this work, we use various computational methods, including molecular dynamics and Wang-Landau Monte Carlo simulations, to study a multi-flavored binary system of micron-sized DNA-functionalized particles modeled implicitly by Fermi-Jagla pairwise interactions. We show how self-assembly of such systems can be controlled in a purely enthalpic manner, and by tuning only the interactions between like particles, demonstrate assembly into various morphologies. Although polymorphism is present over a wide range of pairwise interaction strengths, we show that careful selection of interactions can lead to the generation of pure compositionally ordered crystals. Additionally, we show how the crystal composition changes with the like-pair interaction strengths, and how the solution stoichiometry affects the assembled structures.

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“…If these results were extended to lower-symmetry particles (e.g., tetrahedra), one would imagine an even smaller zone of anisotropy and richer phase diagram, including the possibility of quasicrystal or diamond lattices (20,30,36,39). Due to the highly modular and programmable nature of nucleic acids, the location of these phase transitions can likely be tuned depending on the desired structure, via modulation of the design (e.g., flexibility) (40) or the type of nucleic acid used (e.g., locked nucleic acid or RNA) (41). Beyond defining the zone of anisotropy, this work also establishes a strategy to assemble nonspherical building blocks into a rich set of different phases based on the interplay of the particle and ligand structure.…”

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Exploring the zone of anisotropy and broken symmetries in DNA-mediated nanoparticle crystallization

O’Brien

Girard

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In this work, we present a joint experimental and molecular dynamics simulations effort to understand and map the crystallization behavior of polyhedral nanoparticles assembled via the interaction of DNA surface ligands. In these systems, we systematically investigated the interplay between the effects of particle core (via the particle symmetry and particle size) and ligands (via the ligand length) on crystallization behavior. This investigation revealed rich phase diagrams, previously unobserved phase transitions in polyhedral crystallization behavior, and an unexpected symmetry breaking in the ligand distribution on a particle surface. To understand these results, we introduce the concept of a zone of anisotropy, or the portion of the phase space where the anisotropy of the particle is preserved in the crystallization behavior. Through comparison of the zone of anisotropy for each particle we develop a foundational roadmap to guide future investigations.ver the past decade, major advances in the control of nanoparticle interactions have led to powerful methods to assemble colloidal crystals (1-9). A high degree of structural control can be achieved in these methods if surface-bound ligands are used as nanoscale bonding elements to control the specificity, spacing, and strength of interactions. DNA has emerged as a particularly versatile ligand whose chemically and structurally defined nature can be used to program the symmetry, lattice parameters, and habit of colloidal crystals (1,2,7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The shape of the underlying nanoparticle influences the directionality of DNA interactions, which can result in correlated nanoparticle orientations and predictable crystal symmetries based on geometric considerations (7,13,16,19,20). However, predictive control can be lost if the DNA shell does not preserve the anisotropy of the particle core (13), and thus key questions pertain to (i) the phase space over which predictable directional interactions persist and (ii) the nature of the phase transitions that occur as the anisotropy of the particle disappears. Identifying this "zone of anisotropy" and the broken symmetries that form are critical to establish design rules for work with nonspherical particles and to develop nanostructured materials with controlled properties.Herein, we systematically investigate the phase space encoded by particle symmetry, particle size (L), and DNA length (D) to understand and map where directional interactions persist (Fig. 1). We show that particle symmetry dictates the crystalline states that can be accessed and how easily changes in L and D affect phase transitions between these states, which include transitions in Bravais lattice (i.e., the symmetry of how the particles are arranged within the unit cell) and particle orientation. The concepts introduced herein provide a roadmap to understand and predict particle crystallization behavior toward the construction of functional nanoparticle-based materials.To map the zone of anisotropy in DNA-mediated nan...

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Modular and Chemically Responsive Oligonucleotide “Bonds” in Nanoparticle Superlattices

Cited by 25 publications

References 51 publications

Self-Transfecting Micellar RNA: Modulating Nanoparticle Cell Interactions via High Density Display of Small Molecule Ligands on Micelle Coronas

Self-Transfecting Micellar RNA: Modulating Nanoparticle Cell Interactions via High Density Display of Small Molecule Ligands on Micelle Coronas

Assembly of three-dimensional binary superlattices from multi-flavored particles

Exploring the zone of anisotropy and broken symmetries in DNA-mediated nanoparticle crystallization

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