Plasmid‐Templated Shape Control of Condensed DNA–Block Copolymer Nanoparticles

Jiang, Xiang; Qu, Wei; Pan, Deng; Ren, Yong; Williford, John Michael; Cui, Honggang; Luijten, Erik; Mao, Hai‐Quan

doi:10.1002/adma.201202932

Cited by 118 publications

(145 citation statements)

References 28 publications

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“…Rod-shaped particles may be prepared from various materials, including polymers (19), iron oxide (48), carbon nanotubes (58), DNA/PEG micelles (59), and gold (60) for applications in drug delivery. Rod-shaped particles prepared from these materials will enhance the specificity of tissue-specific targets.…”

Section: Discussionmentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

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

590

507

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Vascular endothelium offers a variety of therapeutic targets for the treatment of cancer, cardiovascular diseases, inflammation, and oxidative stress. Significant research has been focused on developing agents to target the endothelium in diseased tissues. This includes identification of antibodies against adhesion molecules and neovascular expression markers or peptides discovered using phage display. Such targeting molecules also have been used to deliver nanoparticles to the endothelium of the diseased tissue. Here we report, based on in vitro and in vivo studies, that the specificity of endothelial targeting can be enhanced further by engineering the shape of ligand-displaying nanoparticles. In vitro studies performed using microfluidic systems that mimic the vasculature (synthetic microvascular networks) showed that rodshaped nanoparticles exhibit higher specific and lower nonspecific accumulation under flow at the target compared with their spherical counterparts. Mathematical modeling of particle-surface interactions suggests that the higher avidity and specificity of nanorods originate from the balance of polyvalent interactions that favor adhesion and entropic losses as well as shear-induced detachment that reduce binding. In vivo experiments in mice confirmed that shape-induced enhancement of vascular targeting is also observed under physiological conditions in lungs and brain for nanoparticles displaying anti-intracellular adhesion molecule 1 and anti-transferrin receptor antibodies.biodistribution | morphology | SMN | cylinder | drug delivery

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Section: Discussionmentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

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

590

507

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“…20 In collaboration with Mao and co-workers, we previously reported effective shape control of plasmid DNA and polyphosphoramidate (PPA)-based nanoparticles 21,22 and showed that nanoparticle shape correlates with transfection efficiency. To achieve shape control for PEI/siRNA nanoparticles as well, new PEI-based carriers are needed.…”

Section: Introductionmentioning

confidence: 98%

“…These limitations can be overcome by CG simulations based upon a bead-spring model, as employed in investigations on shape control of micellar DNA nanoparticles 21,22 and other coarse-grained studies of DNA condensation by polycations. [23][24][25] In such models, which often use an implicit solvent, the nucleic acids are represented as simple polyanions, which capture sufficient structural properties to provide mechanistic insights, but lack the details that enable quantitative predictions of the binding pattern and dynamics.…”

Section: Introductionmentioning

confidence: 99%

Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

Wei

Luijten

2015

The Journal of Chemical Physics

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All-atom molecular dynamics simulations can provide insight into the properties of polymeric gene-delivery carriers by elucidating their interactions and detailed binding patterns with nucleic acids. However, to explore nanoparticle formation through complexation of these polymers and nucleic acids and study their behavior at experimentally relevant time and length scales, a reliable coarse-grained model is needed. Here, we systematically develop such a model for the complexation of small interfering RNA (siRNA) and grafted polyethyleneimine copolymers, a promising candidate for siRNA delivery. We compare the predictions of this model with all-atom simulations and demonstrate that it is capable of reproducing detailed binding patterns, charge characteristics, and water release kinetics. Since the coarse-grained model accelerates the simulations by one to two orders of magnitude, it will make it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers. C 2015 AIP Publishing LLC. [http://dx

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“…Recent advances in fabrication technologies have enabled generation of shape-specific microparticles and nanoparticles (8-12). These particles, inspired by the diverse, evolutionarily conserved shapes of pathogens and cells, are being used to study the role of carrier shape on cellular internalization, in vivo transport, and organ distribution (6,11,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).Despite these pioneering studies, there remains a significant knowledge gap in our fundamental understanding of the interplay between nanoscale shape and size on cellular internalization, especially for clinically relevant polymer-based hydrophilic nanoparticles. Most in vivo drug delivery and imaging applications have proposed the use of nanoparticles with hydrophilic "stealth" surfaces [often achieved through poly(ethylene glycol) (PEG)-based surface modifications] as well as neutral to anionic surface charge, primarily to allow longer in vivo circulation time by reducing protein adsorption and rapid clearance by the reticuloendothelial system (2, 24-27).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms

Agarwal¹,

Singh

Jurney

et al. 2013

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

377

336

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Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, mammalian epithelial and immune cells preferentially internalize disc-shaped, negatively charged hydrophilic nanoparticles of high aspect ratios compared with nanorods and lower aspect-ratio nanodiscs. Endothelial cells also prefer nanodiscs, however those of intermediate aspect ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and nanorods are internalized more efficiently than their smallest counterparts. Kinetics, efficiency, and mechanisms of uptake are all shape-dependent and cell type-specific. Although macropinocytosis is used by both epithelial and endothelial cells, epithelial cells uniquely internalize these nanoparticles using the caveolae-mediated pathway. Human umbilical vein endothelial cells, on the other hand, use clathrin-mediated uptake for all shapes and show significantly higher uptake efficiency compared with epithelial cells. Using results from both upright and inverted cultures, we propose that nanoparticle internalization is a complex manifestation of three shape-and size-dependent parameters: particle surface-to-cell membrane contact area, i.e., particle-cell adhesion, strain energy for membrane deformation, and sedimentation or local particle concentration at the cell membrane. These studies provide a fundamental understanding on how nanoparticle uptake in different mammalian cells is influenced by the nanoscale geometry and is critical for designing improved nanocarriers and predicting nanomaterial toxicity.cell-uptake mechanism | nanoimprint lithography | drug delivery P olymeric nanoparticles are widely studied for delivering therapeutic and imaging payloads to cells. Understanding how particle properties affect cell uptake is not only critical for designing improved therapeutic and diagnostic agents (1, 2) but also essential for efficient in vitro cell manipulation (3) and evaluating nanomaterial toxicity (4). Nanoparticle uptake by cells has been shown to depend on particle size, surface charge, and material compositions (5-7). Recent advances in fabrication technologies have enabled generation of shape-specific microparticles and nanoparticles (8-12). These particles, inspired by the diverse, evolutionarily conserved shapes of pathogens and cells, are being used to study the role of carrier shape on cellular internalization, in vivo transport, and organ distribution (6,11,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).Despite these pioneering studies, there remains a significant knowledge gap in our fundamental understanding of the interplay between nanoscale shape and size on cellular internalization, especially for clinically relevant polymer-based hydrophilic nanoparticles. Most in vivo drug delivery and imaging applicati...

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Plasmid‐Templated Shape Control of Condensed DNA–Block Copolymer Nanoparticles

Cited by 118 publications

References 28 publications

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms

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