Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules

Jiang, Ying; Tang, Ruixiang; Duncan, Bradley; Jiang, Ziwen; Yan, Bo; Mout, Rubul; Rotello, Vincent M.

doi:10.1002/anie.201409161

Cited by 84 publications

(68 citation statements)

References 53 publications

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“…Nanoparticle mediated biomolecular delivery can occur through either an endocytic or a membrane fusion mechanisms (Figure 1d). 22 We pretreated HeLa cells with inhibitors of endocytosis (chlorpromazine and wortmannin) or cholesterol-dependent membrane fusion (methyl-beta-cyclodextrin (MBCD)), 23 to investigate whether similar mechanisms are involved in Cas9-RNP delivery. After the inhibitor treatment, HeLa cells were incubated with the nanoassemblies, and monitored the delivery by CLSM.…”

Section: Resultsmentioning

confidence: 99%

Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing

et al. 2017

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Genome editing through the delivery of CRISPR/Cas9-ribonulceoprotein (Cas9-RNP) reduces unwanted gene targeting and avoids integrational mutagenesis that can occur through gene delivery strategies. Direct and efficient delivery of Cas9-RNP into the cytosol followed by translocation to the nucleus remains a challenge. Here we report a remarkably high efficient (~90%) direct cytoplasmic/nuclear delivery of Cas9 protein complexed with a guide RNA (sgRNA) through the co-engineering of Cas9 protein and carrier nanoparticles. This construct provides effective (~30%) gene editing efficiency and opens up new opportunities in studying genome dynamics.

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Section: Resultsmentioning

confidence: 99%

Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing

et al. 2017

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“…The microscopic structure of this EDL is difficult to interrogate experimentally [1][2][3][4][5] and is extensively debated in the literature because of its fundamental and technological significance in controlling surface structure [6,7], regulating interfacial reactivity [8] and colloid-colloid interactions [9], governing transport in microfluidics [10] and nanofluidics [11], and mitigating drug-carrier cell interactions [12]. The EDL is also at the heart of many processes of global interest [13], including capacitive deionization of ground water [14,15] and the harnessing of intermittent power sources (e.g., wind and solar) through large-scale electric double-layer capacitors [16].…”

Section: Introductionmentioning

confidence: 99%

Determination of Surface Potential and Electrical Double-Layer Structure at the Aqueous Electrolyte-Nanoparticle Interface

et al. 2016

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The structure of the electrical double layer has been debated for well over a century, since it mediates colloidal interactions, regulates surface structure, controls reactivity, sets capacitance, and represents the central element of electrochemical supercapacitors. The surface potential of such surfaces generally exceeds the electrokinetic potential, often substantially. Traditionally, a Stern layer of nonspecifically adsorbed ions has been invoked to rationalize the difference between these two potentials; however, the inability to directly measure the surface potential of dispersed systems has rendered quantitative measurements of the Stern layer potential, and other quantities associated with the outer Helmholtz plane, impossible. Here, we use x-ray photoelectron spectroscopy from a liquid microjet to measure the absolute surface potentials of silica nanoparticles dispersed in aqueous electrolytes. We quantitatively determine the impact of specific cations (Li þ , Na þ , K þ , and Cs þ ) in chloride electrolytes on the surface potential, the location of the shear plane, and the capacitance of the Stern layer. We find that the magnitude of the surface potential increases linearly with the hydrated-cation radius. Interpreting our data using the simplest assumptions and most straightforward understanding of Gouy-Chapman-Stern theory reveals a Stern layer whose thickness corresponds to a single layer of water molecules hydrating the silica surface, plus the radius of the hydrated cation. These results subject electrical double-layer theories to direct and falsifiable tests to reveal a physically intuitive and quantitatively verified picture of the Stern layer that is consistent across multiple electrolytes and solution conditions.

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“…25 NPSCs consist of an linoleic acid oil core coated in arginine-functionalized gold nanoparticles (Arg-AuNP) that are electrostatically associated with negatively charged biomolecules such as siRNA (Figure 1). Instead of relying on endocytosis to enter cells, NPSCs use an entirely different mechanism, circumventing endosomal entrapment.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous cytosolic delivery of a chemotherapeutic and siRNA using nanoparticle-stabilized nanocapsules

et al. 2016

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We report nanoparticle-stabilized capsules (NPSCs) as a platform for co-delivery of survivin-targeted siRNA and tamoxifen. These capsules feature an inner oil core that provides a carrier for tamoxifen, and coated is coated on the surface with positvely charged nanoparticles self-assembled with siRNA. the multifaceted chemical nature of the NPSC system enables simultaneous delivery of both payloads directly into the cytosol in vitro. NPSC co-delivery of tamoxifen and survivin-targeted siRNA into breast cancer cells disables pathways that inhibit apoptosis, resulting in enhanced breast cell death.

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Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules

Cited by 84 publications

References 53 publications

Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing

Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing

Determination of Surface Potential and Electrical Double-Layer Structure at the Aqueous Electrolyte-Nanoparticle Interface

Simultaneous cytosolic delivery of a chemotherapeutic and siRNA using nanoparticle-stabilized nanocapsules

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