Gold Nanotapes and Nanopinecones in a Quantitative Lateral Flow Assay for the Cancer Biomarker Carcinoembryonic Antigen.

Colorectal cancer is the third most common malignancy and the second leading cause of cancer death globally. Multiple studies have linked levels of carcinoembryonic antigen in patient serum to poor disease prognosis. Hence, the ability to detect low levels of carcinoembryonic antigen has applications in earlier disease diagnosis, assessment, and recurrence monitoring. Existing carcinoembryonic antigen detection methods often require multiple reagents, trained operators, or complex procedures. A method alleviating these issues is the lateral flow assay, a paper-based platform that allows the detection and quantification of target analytes in complex mixtures. The tests are rapid, are point-of-care, possess a long shelf life, and can be stored at ambient conditions, making them ideal for use in a range of settings. Although lateral flow assays typically use spherical gold nanoparticles to generate the classic red signal, recent literature has shown that alternate morphologies to spheres can improve the limit of detection. In this work, we report the application of alternative gold nanoparticle morphologies, gold nanotapes (∼35 nm in length) and gold nanopinecones (∼90 nm in diameter), in a lateral flow assay for carcinoembryonic antigen. In a comparative assay, gold nanopinecones exhibited a ∼2× improvement in the limit of detection compared to commercially available spherical gold nanoparticles for the same antibody loading and total gold content, whereas the number of gold nanopinecones in each test was ∼3.2× less. In the fully optimized test, a limit of detection of 14.4 pg/mL was obtained using the gold nanopinecones, representing a 24-fold improvement over the previously reported gold-nanoparticle-based carcinoembryonic antigen lateral flow assay.

Spectrophotometric Analysis and Optimization of 2D Gold Nanosheet Formation.

Free-standing, 2D gold nanosheets (AuNS) offer broad potential applications from computing to biosensing and healthcare. Such applications, however, require improved control of material growth. We recently reported the synthesis of AuNS only ∼0.47 nm (two atoms) thick, which exhibited very high catalytic activity. The synthesis is a one-pot, seedless procedure in which chloroauric acid is reduced by sodium citrate in the presence of methyl orange (MO). In this study, we use spectrophotometric analysis and TEM imaging to probe AuNS formation and optimize the procedure. Previously, we suggested that MO acted as the confining agent, directing two-dimensional growth of the gold. Here, we provide the first reported analysis of the HAuCl4 and MO reaction. We show that MO is rapidly oxidized to give 4-diazobenzenesulfonic acid, indicating that a complex interplay between HAuCl4, MO, and other reaction products leads to AuNS formation. Time-resolved studies indicate that synthesis time can be significantly reduced from over 12 to 2-3 h. Decreasing the reaction temperature from 20 to 4 °C improved AuNS yield by 16-fold, and the catalytic activity of the optimized material matches that obtained previously. Our elucidation of AuNS formation mechanisms has opened avenues to further improve and tune the synthesis, enhancing the potential applications of ultrathin AuNS.

Hyaluronic-Acid-Tagged Cubosomes Deliver Cytotoxics Specifically to CD44-Positive Cancer Cells.

Delivery of chemotherapy drugs specifically to cancer cells raises local drug doses in tumors and therefore kills more cancer cells while reducing side effects in other tissues, thereby improving oncological and quality of life outcomes. Cubosomes, liquid crystalline lipid nanoparticles, are potential vehicles for delivery of chemotherapy drugs, presenting the advantages of biocompatibility, stable encapsulation, and high drug loading of hydrophobic or hydrophilic drugs. However, active targeting of drug-loaded cubosomes to cancer cells, as opposed to passive accumulation, remains relatively underexplored. We formulated and characterized cubosomes loaded with potential cancer drug copper acetylacetonate and functionalized their surfaces using click chemistry coupling with hyaluronic acid (HA), the ligand for the cell surface receptor CD44. CD44 is overexpressed in many cancer types including breast and colorectal. HA-tagged, copper-acetylacetonate-loaded cubosomes have an average hydrodynamic diameter of 152 nm, with an internal nanostructure based on the space group Im3m. These cubosomes were efficiently taken up by two CD44-expressing cancer cell lines (MDA-MB-231 and HT29, representing breast and colon cancer) but not by two CD44-negative cell lines (MCF-7 breast cancer and HEK-293 kidney cells). HA-tagged cubosomes caused significantly more cell death than untargeted cubosomes in the CD44-positive cells, demonstrating the value of the targeting. CD44-negative cells were equally relatively resistant to both, demonstrating the specificity of the targeting. Cell death was characterized as apoptotic. Specific targeting and cell death were evident in both 2D culture and 3D spheroids. We conclude that HA-tagged, copper-acetylacetonate-loaded cubosomes show great potential as an effective therapeutic for selective targeting of CD44-expressing tumors.

Sub-Nanometer Thick Gold Nanosheets as Highly Efficient Catalysts.

2D metal nanomaterials offer exciting prospects in terms of their properties and functions. However, the ambient aqueous synthesis of atomically-thin, 2D metallic nanomaterials represents a significant challenge. Herein, freestanding and atomically-thin gold nanosheets with a thickness of only 0.47 nm (two atomic layers thick) are synthesized via a one-step aqueous approach at 20 °C, using methyl orange as a confining agent. Owing to the high surface-area-to-volume ratio, abundance of unsaturated atoms exposed on the surface and large interfacial areas arising from their ultrathin 2D nature, the as-prepared Au nanosheets demonstrate excellent catalysis performance in the model reaction of 4-nitrophenol reduction, and remarkable peroxidase-mimicking activity, which enables a highly sensitive colorimetric sensing of H2O2 with a detection limit of 0.11 × 10-6 m. This work represents the first fabrication of freestanding 2D gold with a sub-nanometer thickness, opens up an innovative pathway toward atomically-thin metal nanomaterials that can serve as model systems for inspiring fundamental advances in materials science, and holds potential across a wide region of applications.

Corrigendum: Morphological control of seedlessly-synthesized gold nanorods using binary surfactants (2018 Nanotechnology 29 135601).

Two errors have been found in paragraph 2 of section 2.2. An incorrect volume for the amount of AgNO3 solution added and the order in which solutions were added is wrong.

One-step fabrication of hollow-channel gold nanoflowers with excellent catalytic performance and large single-particle SERS activity.

Hollow metallic nanostructures have shown potential in various applications including catalysis, drug delivery and phototherapy, owing to their large surface areas, reduced net density, and unique optical properties. In this study, novel hollow gold nanoflowers (HAuNFs) consisting of an open hollow channel in the center and multiple branches/tips on the outer surface are fabricated for the first time, via a facile one-step synthesis using an auto-degradable nanofiber as a bifunctional template. The one-dimensional (1D) nanofiber acts as both a threading template as well as a promoter of the anisotropic growth of the gold crystal, the combination of which leads to the formation of HAuNFs with a hollow channel and nanospikes. The synergy of favorable structural/surface features, including sharp edges, open cavity and high-index facets, provides our HAuNFs with excellent catalytic performance (activity and cycling stability) coupled with large single-particle SERS activity (including ∼30 times of activity in ethanol electro-oxidation and ∼40 times of single-particle SERS intensity, benchmarked against similar-sized solid gold nanospheres with smooth surfaces, as well as retaining 86.7% of the initial catalytic activity after 500 cycles in ethanol electro-oxidation). This innovative synthesis gives a nanostructure of the geometry distinct from the template and is extendable to fabricating other systems for example, hollow-channel silver nanoflowers (HAgNFs). It thus provides an insight into the design of hollow nanostructures via template methods, and offers a versatile synthetic strategy for diverse metal nanomaterials suited for a broad range of applications.