Ja-an Annie Ho

Au Nanocube-Directed Fabrication of Au−Pd Core−Shell Nanocrystals with Tetrahexahedral, Concave Octahedral, and Octahedral Structures and Their Electrocatalytic Activity

In this study, we have successfully developed a facile method for the high-yield fabrication of Au-Pd core-shell heterostructures with an unusual tetrahexahedral (THH) morphology using Au nanocubes as the structure-directing cores. The lattice orientations of the Au nanocubes match those of the Pd shells. Structural analysis establishes that the THH nanocrystals are bounded by high-index {730} facets. A substantial lattice mismatch between Au and Pd, oxidative etching in the presence of chloride and oxygen, the use of cetyltrimethylammonium chloride (CTAC) surfactant, and the reaction temperature (30-60 °C) were identified to be key factors facilitating the formation of the THH core-shell nanocrystals. Intermediate products have also been examined to follow the growth process. By selecting cubic gold cores with sizes of 30-70 nm and varying the volume of the gold core solution used, THH Au-Pd core-shell nanocrystals with continuously adjustable sizes from 56 to 124 nm can be readily obtained. Their UV-vis spectra display progressive red-shifted bands. Interestingly, novel concave octahedral and octahedral Au-Pd core-shell nanocrystals can be prepared by lowering the reaction temperature and prolonging the reaction time. The concave octahedra show depressions on all the {111} faces. Electrocatalytic activity of the three Au-Pd core-shell structures for the oxidation of ethanol has been investigated. The THH nanocrystals with entirely high-index {730} facets were found to exhibit the best electrocatalytic activity. These size-tunable THH Au-Pd core-shell nanocrystals may be valuable for catalyzing other organic reactions.

DOPA-mediated reduction allows the facile synthesis of fluorescent gold nanoclusters for use as sensing probes for ferric ions.

In this paper, we describe a simple one-pot method, employing l-3,4-dihydroxyphenylalanine (L-DOPA) as a reducing/capping reagent, for the synthesis of fluorescent gold nanoclusters (AuNCs). Within a short reaction time of 15 min (excluding the time required for purification), this strategy allows the fabrication of homogeneous AuNCs having the capability to sense ferric ions (Fe(3+)). The as-prepared AuNCs exhibited a fluorescence emission at 525 nm and a quantum yield of 1.7%. On the basis of an aggregation-induced fluorescence quenching mechanism, these fluorescent AuNCs offer acceptable sensitivity, high selectivity, and a limit of detection of 3.5 μM for the determination of Fe(3+) ions, which is lower than the maximum level (0.3 mg L(-1), equivalent to 5.4 μM) of Fe(3+) permitted in drinking water by the U.S. Environmental Protection Agency.

Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles.

Nanoparticle-assisted drug delivery has been emerging as an active research area in recent years. The in vivo biodistribution of nanoparticle and its following mechanisms of biodegradation and/or excretion determine the feasibility and applicability of such a nano-delivery platform in the practical clinical translation. In this work we report the synthesis of the highly positive charge, near-infrared fluorescent mesoporous silica nanoparticles (MSNs) that demonstrate rapid hepatobiliary excretion, for use as traceable drug delivery platforms of high capacity. MSNs were incorporated with near-infrared fluorescent dye indocyanine green (ICG) via covalent or ionic bonding, to derive comparable constructs of significantly different net surface charge. In vivo fluorescence imaging and subsequent inductively coupled plasma-mass spectroscopy of harvested tissues, urine, and feces revealed markedly different uptake and elimination behaviors between the two conjugations; with more highly charged moieties (+34.4 mV at pH 7.4) being quickly excreted from the liver into the gastrointestinal tract, while less charged moieties (-17.6 mV at pH 7.4) remained sequestered within the liver. Taken together, these findings suggest that charge-dependent adsorption of serum proteins greatly facilitates the hepatobiliary excretion of silica nanoparticles, and that nanoparticle residence time in vivo can be regulated by manipulation of surface charge.

Biofunctionalized Phospholipid-Capped Mesoporous Silica Nanoshuttles for Targeted Drug Delivery: Improved Water Suspensibility and Decreased Nonspecific Protein Binding

A main challenge in nanobiomedicine is the engineering of nanostructures or nanomaterials that can efficiently encapsulate drugs at high load, cross cell membranes, and controllably release their cargo at target sites. Although mesoporous silica nanoparticles (MSNs) are safe, versatile, and promising carrier materials for targeted drug delivery, their aggregation phenomena under physiological conditions (or salt-containing environments) and their nonspecific binding in protein-containing solutions (or serum) limit their applications in biological science and biomedicine. To address this challenge, we have developed a novel delivery system, termed a nanoshuttle, comprising a nanoscale PEGylated-phospholipid coating and 13-(chlorodimethylsilylmethyl)heptacosane-derivatized MSNs, in which therapeutic or imaging agents may be trapped and ligand-assisted targeted delivery may be achieved through surface functionalization of the phospholipids. As a proof of concept in this study, we selected fluorescein isothiocyanate and folate as the imaging tracer and targeted ligand, respectively. Relative to the bare MSNs, the lipid-capped MSNs exhibited superior suspensibility in phosphate-buffered saline and much lower nonspecific binding in vitro. Furthermore, enhanced specific cellular uptake by Hela cells occurred after administering the folate-sensitized phospholipid-capped MSNs. Our results suggest that these highly versatile multifunctional MSNs are promising vectors for nanomedicine applications.

Diagnostic detection of human lung cancer-associated antigen using a gold nanoparticle-based electrochemical immunosensor.

The development of rapid and sensitive methods for the detection of immunogenic tumor-associated antigen is important not only for understanding their roles in cancer immunology but also for the development of clinical diagnostics. Alpha-enolase (ENO1), a p48 molecule, is widely distributed in a variety of tissues, whereas gamma-enolase (ENO2) and beta-enolase (ENO3) are found exclusively in neuron/neuroendocrine and muscle tissues, respectively. Because ENO1 has been correlated with small cell lung cancer, nonsmall cell lung cancer, and head and neck cancer, it can be used as a potential diagnostic marker for lung cancer. In this study, we developed a simple, yet novel and sensitive, electrochemical sandwich immunosensor for the detection of ENO1; it operates through physisorption of anti-ENO1 monoclonal antibody on polyethylene glycol-modified disposable screen-printed electrode as the detection platform, with polyclonal secondary anti-ENO1-tagged, gold nanoparticle (AuNP) congregates as electrochemical signal probes. The immunorecognition of the sample ENO1 by the congregated AuNP@antibody occurred on the surface of the electrodes; the electrochemical signal from the bound AuNP congregates was obtained after oxidizing them in 0.1 M HCl at 1.2 V for 120 s, followed by the reduction of AuCl(4-) in square wave voltammetry (SWV) mode. The resulting sigmoidally shaped dose-response curves possessed a linear dynamic working range from 10(-8) to 10(-12) g/mL. This AuNP congregate-based assay provides an amplification approach for detecting ENO1 at trace levels, leading to a detection limit as low as 11.9 fg (equivalent to 5 microL of a 2.38 pg/mL solution).

Carbon Nanoparticle-Enhanced Immunoelectrochemical Detection for Protein Tumor Marker with Cadmium Sulfide Biotracers

We have developed a sensitive electrochemical immunoassay system for the detection of a protein tumor marker, carcinoembryonic antigen (CEA), that is based on a carbon nanoparticle (CNP)/poly(ethylene imine) (PEI)-modified screen-printed graphite electrode (CNP-PEI/SPGE) covered with anti-CEA antibodies. The signal amplification strategy--using CdS nanocrystals as biotracers and CNPs to enhance electron transfer--improves the sensitivity and detection limit for CEA, suggesting that this system holds promise for development into a point-of-care or disposable home-care self-diagnostic tool. This biosensor is based on a sandwich complex immunoassay, which we assembled from sequential layers of the anti-CEA antibody (alphaCEA) on CNP-PEI/SPGE, the CEA sample, and the CdS nanocrystal quantum dots (QDs) sensitized with alphaCEA (alphaCEA-CdS QD). We used square wave anodic stripping voltammetry (SWASV) to amplify the signal current response obtained from the dissolved alphaCEA-CdS QDs. The calibration curve for CEA concentration was linear in the range of 0.032-10 ng/mL; the detection limit (estimated as the mean of the blank sample plus three times the standard deviation obtained on the blank sample) was 32 pg/mL (equivalent to 160 fg in a 5 microL sample). This method is suitably precise and sensitive to function as a means of determining urinary CEA, which is a better marker than serum CEA for the early detection of urothelial carcinoma.

Disposable electrochemical immunosensor for carcinoembryonic antigen using ferrocene liposomes and MWCNT screen-printed electrode

Disposable electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA) in saliva and serum was developed. Monoclonal anti-CEA antibodies (alphaCEA) were covalently immobilized on polyethyleneimine wrapped multiwalled carbon nanotubes screen-printed electrode. A sandwich immunoassay was performed with CEA and alphaCEA tagged ferrocene carboxylic acid encapsulated liposomes (alphaCEA-FCL). The square wave voltammetry (SWV) was employed to analyze faradic redox responses of the released ferrocene carboxylic acid from the immunoconjugated liposomes on the electrode surface. The magnitude of the SWV peak current was directly related to the concentration of CEA. The calibration curve for CEA concentration was in the range of 5 x 10(-12) to 5 x 10(-7)gmL(-1) with a detection limit of 1 x 10(-12)gmL(-1) (S/N=3). This method provides a high precise and sensitive determination of CEA in human blood serum and saliva samples.

Attomole DNA Electrochemical Sensor for the Detection of Escherichia coli O157

Enterohemorrhagic Escherichia coli O157, a verocytotoxin (VT1/2)-producing pathogen, can be deadly because it can induce acute or chronic renal failure. To speed up the clinical diagnosis of related syndromes caused by E. coli O157, there is an urgent need for rapid, simple, and reliable analytical tools for its quantitation. In this study, we developed a novel electrochemical competitive genosensor, featuring gold-electrodeposited screen-printed electrodes (nanoAu/SPE) modified with a self-assembled monolayer of thiol-capped single-stranded DNA (capture probe), for the detection of the rfbE gene, which is specific to E. coli O157. This assay functions based on competition between the target gene (complementary to the capture probe DNA) and reporter DNA-tagged, hexaammineruthenium(III) chloride-encapsulated liposomes. The current signal of the released liposomal Ru(NH(3))(6)(3+) was measured using square wave voltammetry, yielding a sigmoidally shaped dose-response curve whose linear portion was over the range from 1 to 10(6) fmol. This liposomal competitive assay provides an amplification route for the detection of the rfbE gene at ultratrace levels; indeed, we could detect as little as 0.75 amol of the target rfbE DNA (equivalent to the amount present in 5 microL of a 0.15 pM solution).

Nanotheranostics--a review of recent publications.

Theranostics is referred to as a treatment strategy that combines therapeutics with diagnostics, aiming to monitor the response to treatment and increase drug efficacy and safety, which would be a key part of personalized medicine and require considerable advances in predictive medicine. Theranostics associates with both a diagnosis that tests patients for possible reactions to taking new medication and targeted drug delivery based on the test results. Emerging nanotechnology provides a great deal of opportunity to design and develop such combination agents, permitting the delivery of therapeutics and concurrently allowing the detection modality to be used not only before or after but also throughout the entire treatment regimen. The introduction of nanotheranostics into routine health care has still a long way to go, since evaluations on cytotoxicity, genotoxicity, and immunotoxicity of prospective nanotheranostics, demonstration of cost-effectiveness, and availability of appropriate accessible testing systems are still required. An extensive review, from a chemistry point of view, of the recent development of nanotheranostics and its in vitro and in vivo applications are herein presented.

Electrochemical immunosensor for multiplexed detection of food-borne pathogens using nanocrystal bioconjugates and MWCNT screen-printed electrode

Bacterial food poisoning is an ever-present threat that can be prevented with proper care and handling of food products. A disposable electrochemical immunosensor for the simultaneous measurements of common food pathogenic bacteria namely Escherichia coli O157:H7 (E. coli), campylobacter and salmonella were developed. The immunosensor was fabricated by immobilizing the mixture of anti-E. coli, anti-campylobacter and anti-salmonella antibodies with a ratio of 1:1:1 on the surface of the multiwall carbon nanotube-polyallylamine modified screen printed electrode (MWCNT-PAH/SPE). Bacteria suspension became attached to the immobilized antibodies when the immunosensor was incubated in liquid samples. The sandwich immunoassay was performed with three antibodies conjugated with specific nanocrystal (α-E. coli-CdS, α-campylobacter-PbS and α-salmonella-CuS) which has releasable metal ions for electrochemical measurements. The square wave anodic stripping voltammetry (SWASV) was employed to measure released metal ions from bound antibody nanocrystal conjugates. The calibration curves for three selected bacteria were found in the range of 1×10(3)-5×10(5) cells mL(-1) with the limit of detection (LOD) 400 cells mL(-1) for salmonella, 400 cells mL(-1) for campylobacter and 800 cells mL(-1) for E. coli. The precision and sensitivity of this method show the feasibility of multiplexed determination of bacteria in milk samples.