Abstract This paper describes the creation of hybrid surfaces containing cationic nanoparticles and biocompatible PEG (polyethylene glycol) brushes that manipulate bacterial adhesion for potential diagnostic and implant applications.
A nanoparticle design featuring pH-responsive alkoxyphenyl acylsulfonamide ligands is reported herein. As a result of ligand structure, this nanoparticle is neutral at pH 7.4, becoming positively charged at tumor pH (<6.5). The...
moreA nanoparticle design featuring pH-responsive alkoxyphenyl acylsulfonamide ligands is reported herein. As a result of ligand structure, this nanoparticle is neutral at pH 7.4, becoming positively charged at tumor pH (<6.5). The particle uptake and cytotoxicity increase over this pH range. This pH-controlled uptake and toxicity makes this particle a promising tool for tumor selective therapy.
We describe a method for quantitative monitoring of subcellular protein trafficking using nanoparticle-stabilized nanocapsules for protein delivery. This method provides rapid delivery of the protein into the cytosol, eliminating...
moreWe describe a method for quantitative monitoring of subcellular protein trafficking using nanoparticle-stabilized nanocapsules for protein delivery. This method provides rapid delivery of the protein into the cytosol, eliminating complications from protein homeostasis processes found with cellularly expressed proteins. After delivery, nuclear protein trafficking was followed by real time microscopic imaging. Quantitative analyses of the accumulation percentage and the import dynamics of the nuclear protein trafficking, demonstrate the utility of this method for studying intracellular trafficking systems.
Host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparticles (AuNPs) have been quantified using isothermal titration calorimetry. AuNPs were functionalized with ligands containing tertiary or...
moreHost-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparticles (AuNPs) have been quantified using isothermal titration calorimetry. AuNPs were functionalized with ligands containing tertiary or quaternary benzylamine derivatives, with electron donating or withdrawing groups at the para position of the benzene ring. Analysis of binding interactions reveals that functional groups at the para position have no significant effect on binding constant. However, headgroups bearing a permanent positive charge increased the binding of AuNPs to CB[7] ten-fold compared to monomethyl counterparts.
Optical spectroscopic methods do not routinely provide information on higher order hierarchical structure (tertiary/quaternary) of biological macromolecules and assemblies. This necessitates the use of time-consuming and material...
moreOptical spectroscopic methods do not routinely provide information on higher order hierarchical structure (tertiary/quaternary) of biological macromolecules and assemblies. This necessitates the use of time-consuming and material intensive techniques, such as protein crystallography, NMR, and electron microscopy. Here we demonstrate a spectroscopic phenomenon, superchiral polarimetry, which can rapidly characterize ligand-induced changes in protein higher order (tertiary/quaternary) structure at the picogram level, which is undetectable using conventional CD spectroscopy. This is achieved by utilizing the enhanced sensitivity of superchiral evanescent fields to mesoscale chiral structure.
Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst...
moreBioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
Spin or drop coated solutions of ligand-coated nanoparticles act as a novel type of ebeam resist into which functional nanostructures can be produced in a direct-write process (Y. Ofir et al, Adv. Mater. 20, 2561-2566 (2008)). Thin films...
moreSpin or drop coated solutions of ligand-coated nanoparticles act as a novel type of ebeam resist into which functional nanostructures can be produced in a direct-write process (Y. Ofir et al, Adv. Mater. 20, 2561-2566 (2008)). Thin films were produced by this method from a set of resists in which the size of the Au nanoparticles and ligand length were
Bacterial biofilms are widely associated with persistent infections. High resistance to conventional antibiotics and prevalent virulence makes eliminating these bacterial communities challenging therapeutic targets. We describe here the...
moreBacterial biofilms are widely associated with persistent infections. High resistance to conventional antibiotics and prevalent virulence makes eliminating these bacterial communities challenging therapeutic targets. We describe here the fabrication of a nanoparticle-stabilized capsule with a multicomponent core for the treatment of biofilms. The peppermint oil and cinnamaldehyde combination that comprises the core of the capsules act as potent antimicrobial agents. An in situ reaction at the oil/water interface between the nanoparticles and cinnamaldehyde structurally augments the capsules to efficiently deliver the essential oil payloads, effectively eradicating biofilms of clinically isolated pathogenic bacteria strains. In contrast to their antimicrobial action, the capsules selectively promoted fibroblast proliferation in a mixed bacteria/mammalian cell system making them promising for wound healing applications.
Gold nanorods (GNRs) are important platforms for biosensing and drug delivery. As for most nanomaterials, appropriate coatings such as polyethylene glycol (PEG) are needed to stabilize GNRs within biological fluids. We show here that the...
moreGold nanorods (GNRs) are important platforms for biosensing and drug delivery. As for most nanomaterials, appropriate coatings such as polyethylene glycol (PEG) are needed to stabilize GNRs within biological fluids. We show here that the interactions of GNRs with proteins can be finely modulated through surface modification using PEG-containing chains bearing charged headgroups. Interestingly, introduction of amino or carboxylate groups produces relevant and differential changes in GNR interactions with three representative proteins: lysozyme, cytochrome c, and bovine serum albumin. These effects were explored through the direct monitoring of plasmonic bands of the GNRs and are supported by independent dynamic light scattering (DLS) and circular dichroism (CD) determinations. Notably, GNR-protein interactions observed for these charged GNRs can be almost completely reversed by salt addition. These observations demonstrate the importance of electrostatic effects in governing GNR-prot...
Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physico-chemical properties of small molecule and...
moreCombination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physico-chemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed a higher cytotoxicity of than either of the single agent NPSCs, with synergistic action established using combination index values.
This work examines how the antimicrobial (killing) activity of net-negative surfaces depends on the presentation of antimicrobial cationic functionality: distributed versus clustered, and flat clusters versus raised clusters....
moreThis work examines how the antimicrobial (killing) activity of net-negative surfaces depends on the presentation of antimicrobial cationic functionality: distributed versus clustered, and flat clusters versus raised clusters. Specifically, the ability to kill Staphylococcus aureus by sparsely distributed 10 nm cationic nanoparticles, immobilized on a negative surface and backfilled with a PEG (polyethylene glycol) brush, was compared with that for a dense layer of the same immobilized nanoparticles. Additionally, sparsely distributed 10 nm poly-L-lysine (PLL) coils, adsorbed to a surface to produce flat cationic "patches" and backfilled with a PEG brush were compared to a saturated adsorbed layer of PLL. The latter resembled classical uniformly cationic antimicrobial surfaces. The protrusion of the cationic clusters substantially influenced killing but the surface concentration of the clusters had minor impact, as long as bacteria adhered. When surfaces were functionalized...
The role of nanoparticle surface hydrophobicity on its hemolytic property is established in the absence and the presence of plasma proteins. Significantly, the formation of plasma protein corona on NP surface protects red blood cells from...
moreThe role of nanoparticle surface hydrophobicity on its hemolytic property is established in the absence and the presence of plasma proteins. Significantly, the formation of plasma protein corona on NP surface protects red blood cells from both hydrophilic and hydrophobic NP-mediated hemolysis.
Low-cost diagnostics for drinking water contamination have the potential to save millions of lives. We report a method that uses inkjet printing to copattern an enzyme-nanoparticle sensor and substrate on a paper-based test strip for...
moreLow-cost diagnostics for drinking water contamination have the potential to save millions of lives. We report a method that uses inkjet printing to copattern an enzyme-nanoparticle sensor and substrate on a paper-based test strip for rapid detection of bacteria. A colorimetric response is generated on the paper substrate that allows visual detection of contamination without the need for expensive instrumentation. These strips demonstrate a viable nanomanufacturing strategy for low-cost bacterial detection.
This study has shown that easily oxidisable TTF units form charge-transfer (C-T) complexes with 7 which have the largest reported association constants to date. Replacing the sulfur of the TTF unit with selenium or extending the...
moreThis study has shown that easily oxidisable TTF units form charge-transfer (C-T) complexes with 7 which have the largest reported association constants to date. Replacing the sulfur of the TTF unit with selenium or extending the conjugated link between the two dithiole rings reduces the Ka of the complex relative to the parent derivative.
The formation of hydrophilic modified disubstituted para-polyphenyleneethylene (PPE) nanoparticles (NP) complexes in aqueous media and their assemblies have been investigated. Both PPEs and gold NPs are electro-optically active....
moreThe formation of hydrophilic modified disubstituted para-polyphenyleneethylene (PPE) nanoparticles (NP) complexes in aqueous media and their assemblies have been investigated. Both PPEs and gold NPs are electro-optically active. Controlling their association would allow formation of electro-optical tunable responsive materials. Small Angle Neutron Scattering (SANS) in conjunction with Atomic Force Microscopy (AFM) has been used to characterize the structures of the complexes formed. SANS studies have shown that spherical core shell NP-P complexes are formed in dilute solutions, with the gold NPs surrounded by almost fully stretched out PPE chains. With increasing the concentration of the NP-PPE complex in solution chains which consist of the basic core-shell aggregated are observed. These NP-PPE complexes were allowed to assemble at a solid surface. While the basic building block, observed by AFM, remains spherical, they assemble in different ways from random 2-d arrays to cable lik...
Nanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilization for improved stability in bioprocessing. In this work we demonstrate the use of a hierarchical assembly immobilization strategy to enhance...
moreNanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilization for improved stability in bioprocessing. In this work we demonstrate the use of a hierarchical assembly immobilization strategy to enhance the physicochemical properties and stability of lipase B from Candida antarctica (CaLB). CaLB was complexed with iron oxide nanoparticles followed by interfacial assembly at the surface of an oil-in-water emulsion. Subsequent ring opening polymerization of the oil provided cross-linked microparticles that displayed an increase in catalytic efficiency when compared to the native enzyme and Novozym 435. The hierarchical immobilized enzyme assembly showed no leakage from the support in 50% acetonitrile and could be magnetically recovered across five cycles. Immobilized lipase exhibited enhanced thermal and pH stability, providing 72% activity retention after 24 h at 50 °C (pH 7.0) and 62% activity retention after 24 h at pH 3.0 (30 °C); conditions resulting in complete deactivation of the native lipase.
Multi-functional gold nanoparticles have been demonstrated to be highly stable and versatile scaffolds for drug delivery due to their unique size, coupled with their chemical and physical properties. The ability to tune the surface of the...
moreMulti-functional gold nanoparticles have been demonstrated to be highly stable and versatile scaffolds for drug delivery due to their unique size, coupled with their chemical and physical properties. The ability to tune the surface of the particle provides access to cell-specific targeting and controlled drug release. This chapter describes current developments in the area of drug delivery using gold nanoparticles as delivery vehicles for multiple therapeutic purposes.
Screening methods that use traditional genomic, transcriptional, proteomic and metabonomic signatures to characterize drug mechanisms are known. However, they are time consuming and require specialized equipment. Here, we present a...
moreScreening methods that use traditional genomic, transcriptional, proteomic and metabonomic signatures to characterize drug mechanisms are known. However, they are time consuming and require specialized equipment. Here, we present a high-throughput multichannel sensor platform that can profile the mechanisms of various chemotherapeutic drugs in minutes. The sensor consists of a gold nanoparticle complexed with three different fluorescent proteins that can sense drug-induced physicochemical changes on cell surfaces. In the presence of cells, fluorescent proteins are rapidly displaced from the gold nanoparticle surface and fluorescence is restored. Fluorescence 'turn on' of the fluorescent proteins depends on the drug-induced cell surface changes, generating patterns that identify specific mechanisms of cell death induced by drugs. The nanosensor is generalizable to different cell types and does not require processing steps before analysis, offering an effective way to expedite...
Engineering of nanoparticle surface functionality provides controlled interactions with biomolecules such as cell membrane lipids, proteins and nucleic acids. Concurrently, this surface chemistry control also opens up new avenues for...
moreEngineering of nanoparticle surface functionality provides controlled interactions with biomolecules such as cell membrane lipids, proteins and nucleic acids. Concurrently, this surface chemistry control also opens up new avenues for improving mass spectral analyses. In this Minireview, we highlight some of the emerging work that integrates surface-engineered nanoparticles with mass spectrometry to improve the analysis of a wide variety of chemical and biological systems.
Du, K., Knutson, CR, Glogowski, E., McCarthy, KD, Shenhar, R., Rotello, VM, Tuominen, MT, Emrick, T., Russell, TP and Dinsmore, AD (2009), Self-Assembled Electrical Contact to Nanoparticles Using Metallic Droplets. Small, 5: 19741977....
moreDu, K., Knutson, CR, Glogowski, E., McCarthy, KD, Shenhar, R., Rotello, VM, Tuominen, MT, Emrick, T., Russell, TP and Dinsmore, AD (2009), Self-Assembled Electrical Contact to Nanoparticles Using Metallic Droplets. Small, 5: 19741977. doi: 10.1002/smll. 200900203
Synergistic dipole-dipole and hydrogen-bonding interactions are used to assemble nanostructured materials. Precipitation of a hydrogen-bonding donor-acceptor molecule 8-[[p-[bis(ethyl)amino]phenyl]azo]-isobutylflavin (ABFL) yields...
moreSynergistic dipole-dipole and hydrogen-bonding interactions are used to assemble nanostructured materials. Precipitation of a hydrogen-bonding donor-acceptor molecule 8-[[p-[bis(ethyl)amino]phenyl]azo]-isobutylflavin (ABFL) yields nanowires approximately 50-150 nm in diameter and lengths of several millimeters. Precipitation of the non-hydrogen-bonding analog, methylated ABFL (MABFL), generates micrometer-sized hexagonal platelets that are 5-10 microm in length, 1-5 microm in width, and 0.1-0.5 microm thick. The structural similarity of the two molecules allows intermediate morphologies to be formed via co-precipitation. Doping experiments demonstrate efficient control over nanowire length and diameter due to the disruption of the hydrogen bonding within the nanowires.
Catalytically active iron oxide nanoparticles are used as recognition elements and signal amplifiers for the array-based colorimetric sensing of proteins. Interactions between cationic monolayers on the Fe(3) O(4) NPs and analyte proteins...
moreCatalytically active iron oxide nanoparticles are used as recognition elements and signal amplifiers for the array-based colorimetric sensing of proteins. Interactions between cationic monolayers on the Fe(3) O(4) NPs and analyte proteins differentially modulates the peroxidase-like activity of Fe(3) O(4) NPs, affording catalytically amplified colorimetric signal patterns that enable the detection and identification of proteins at 50 nM.
ABSTRACT Dendronized gold nanoparticles (AuNPs) are effective nanocarriers for small interfering RNA (siRNA) delivery. Electrostatic condension of these AuNPs with siRNA provides efficient silencing (∼50%) without cytotoxicity.
Efficient binding of biomacromolecular surfaces by synthetic systems requires the effective presentation of complementary elements over large surface areas. We demonstrate here the use of mixed monolayer protected gold clusters (MMPCs) as...
moreEfficient binding of biomacromolecular surfaces by synthetic systems requires the effective presentation of complementary elements over large surface areas. We demonstrate here the use of mixed monolayer protected gold clusters (MMPCs) as scaffolds for the binding and inhibition of chymotrypsin. In these studies anionically functionalized amphiphilic MMPCs were shown to inhibit chymotrypsin through a two-stage mechanism featuring fast reversible inhibition followed by a slower irreversible process. This interaction is very efficient, with a K(i)(app) = 10.4 +/- 1.3 nM. The MMPC-protein complex was characterized by CD, demonstrating an almost complete denaturation of the enzyme over time. Dynamic light scattering studies confirm that inhibition proceeds without substantial MMPC aggregation. The electrostatic nature of the engineered interactions provides a level of selectivity: little or no inhibition of function was observed with elastase, beta-galactosidase, or cellular retinoic acid binding protein.
