Metastatic disease is usually identified by performing biopsies of solid metastatic tumors. This is often late in the disease, however, and it's better to identify metastatic disease earlier (such as by detecting CTCs) so that treatment can possibly be more effective.

More info from the press release:

In a study published this month in the journal Angewandte Chemie, the UCLA team developed a 1-by-2-centimeter silicon chip that is covered with densely packed nanopillars and looks like a shag carpet. To test cell-capture performance, researchers incubated the nanopillar chip in a culture medium with breast cancer cells. As a control, they performed a parallel experiment with a cell-capture method that uses a chip with a flat surface. Both structures were coated with anti-EpCAM, an antibody protein that can help recognize and capture tumor cells.

The researchers found that the cell-capture yields for the UCLA nanopillar chip were significantly higher; the device captured 45 to 65 percent of the cancer cells in the medium, compared with only 4 to 14 percent for the flat device.

Read the press release here...

Read the abstract here...

CTC flashbacks: Microchips for Tumor Detection, CellTraffix Aims to Cleanse Blood of CA, Collect Stem Cells, Watching Circulating Tumor Cell Count Helps Predict Breast Cancer Development

For their recent study, the team focused primarily on characterizing quantum dot properties, contrasting them with other imaging techniques. In one example, they employed quantum dots designed to target a specific type of human red blood cell protein that forms part of a network structure in the cell’s inner membrane. When these proteins cluster together in a healthy cell, the network provides mechanical flexibility to the cell so it can squeeze through narrow capillaries and other tight spaces. But when the cell gets infected with the malaria parasite, the structure of the network protein changes.

“Because the clustering mechanism is not well understood, we decided to examine it with the dots,” says NIAID biophysist Fuyuki Tokumasu. “We thought if we could develop a technique to visualize the clustering, we could learn something about the progress of a malaria infection, which has several distinct developmental stages.”

The team’s efforts revealed that as the membrane proteins bunch up, the quantum dots attached to them are induced to cluster themselves and glow more brightly, permitting scientists to watch as the clustering of proteins progresses. More broadly, the team found that when quantum dots attach themselves to other nanomaterials, the dots’ optical properties change in unique ways in each case. They also found evidence that quantum dot optical properties are altered as the nanoscale environment changes, offering greater possibility of using quantum dots to sense the local biochemical environment inside cells.

Image: Human red blood cells, in which membrane proteins are targeted and labeled with quantum dots, reveal the clustering behavior of the proteins. The number of purple features, which indicate the nuclei of malaria parasites, increases as malaria development progresses. The NIST logo at bottom was made by a photo lithography technique on a thin film of quantum dots, taking advantage of the property that clustered dots exhibit increased photoluminescence. (White bars: 1 μm; red: 10 μm.)

Press release: Small Nanoparticles Bring Big Improvement to Medical Imaging ...

Abstract in WIREs Nanomedicine and Nanobiotechnology: Probing dynamic fluorescence properties of single and clustered quantum dots toward quantitative biomedical imaging of cells

Vladimir Zharov, director of the Phillips Classic Laser and Nanomedicine Laboratory at UAMS, said his team of researchers can inject a cocktail of magnetic and gold nanoparticles with a special biological coating into the bloodstream to target circulating tumor cells. A magnet attached to the skin above peripheral blood vessels can then capture the cells.

Once the tumor cells are targeted and captured by the magnet, they can either be microsurgically removed from vessels for further genetic analysis or can be noninvasively eradicated directly in blood vessels by laser irradiation through the skin that is still safe for normal blood cells.

A second related discovery by Zharov’s team was published in Cancer Research in October. It demonstrated that periodic laser irradiation of blood vessels decreases the level of circulating metastatic tumor cells more than 10 times and eventually led to an interruption of metastasis development in distant organs.

Press release: Nanotechnology Team Captures Tumor Cells in Bloodstream ...

Abstract in Nature Nanotechnology: In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells

Abstract in Cancer Research: In vivo, Noninvasive, Label-Free Detection and Eradication of Circulating Metastatic Melanoma Cells Using Two-Color Photoacoustic Flow Cytometry with a Diode Laser

From the abstract in Nature Nanotechnology:

Here, we show that cobalt-chromium nanoparticles (29.5 plusminus 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.

Abstract in Nature Nanotechnology...

(hat tip: POPSCI)

Image: Optical image of cobalt nanoparticles onto HOPG substrate by victorpuntes on Flickr...

To learn more about the journal's review articles check out this statement by Institute of Physics, or head to the following open access papers:

Progress in applications of magnetic nanoparticles in biomedicine by Kevin O'Grady

Progress in applications of magnetic nanoparticles in biomedicine by Q A Pankhurst, N K T Thanh, S K Jones and J Dobson

Progress in the preparation of magnetic nanoparticles for applications in biomedicine by A G Roca, R Costo, A F Rebolledo, S Veintemillas-Verdaguer, P Tartaj, T González-Carreño, M P Morales and C J Serna

Progress in functionalization of magnetic nanoparticles for applications in biomedicine by Catherine C Berry

Image: Map showing magnetic flux lines for nickel nanoparticles. ... (Brookhaven NL)

“We are very excited about the prospects this research opens up for nanotechnology,” said Lieber, Mark Hyman Jr. Professor of Chemistry in Harvard’s Faculty of Arts and Sciences. “For example, our nanostructures make possible integration of active devices in nanoelectronic and photonic circuits, as well as totally new approaches for extra- and intracellular biological sensors. This latter area is one where we already have exciting new results, and one we believe can change the way much electrical recording in biology and medicine is carried out.”

Lieber and Tian’s approach involves the controlled introduction of triangular “stereocenters” – essentially, fixed 120-degree joints – into nanowires, structures that have previously been rigidly linear. These stereocenters, analogous to the chemical hubs found in many complex organic molecules, introduce kinks into 1-D nanostructures, transforming them into more complex forms.

The researchers were able to introduce stereocenters as nanowires, which are self-assembled. The researchers halted growth of the 1-D nanostructures for 15 seconds by removing key gaseous reactants from the chemical brew in which the process was taking place, replacing these reactants after joints had been introduced into the nanostructures. This approach resulted in a 40 percent yield of bent nanowires, which can then be purified to achieve higher yields.

“The stereocenters appear as kinks, and the distance between kinks is completely controlled,” said Tian, a research assistant in Harvard’s Department of Chemistry and Chemical Biology. “Moreover, we demonstrated the generality of our approach through synthesis of 2-D silicon, germanium, and cadmium sulfide nanowire structures.”

The research by Lieber and Tian is the latest in the years-long efforts by scientists to control the composition and structure of nanowires during synthesis. Despite advances in these areas, the ability to control the design and growth of self-assembling nanostructures has been limited. Lieber and Tian’s work takes the formation of 2-D nanostructures a step further by enabling the introduction of electronic devices at the stereocenters.

“An important concept that emerged from these studies is that of introducing functionality at defined nanoscale points for the first time – in other words, nanodevices that can ‘self-label,’ ” Lieber said. “We illustrated this novel capability by the insertion of p–n diodes and field-effect transistors precisely at the stereocenters.”

Such self-labeled structures could open up the possibility of introducing nanoelectronics, photodetectors, or biological sensors into complex nanoscale structures.

Full story: Nanowires go 2-D, 3-D...

Abstract in Nature Nanotechnology: Single-crystalline kinked semiconductor nanowire superstructures

From the article abstract in Science:

Optical probes of heterogeneous catalytic reactions can be valuable tools for optimization and process control in that they can operate under realistic conditions, but often these probes lack sensitivity. We have developed a plasmonic sensing method for such reactions based on arrays of nanofabricated gold disks, covered by a thin (~10 nm) coating (catalyst support) on which the catalyst is deposited. The sensing particles monitor changes in surface coverage of reactants (below 0.1 monolayers) during catalytic reaction through peak shifts in the optical extinction spectrum. Sensitivities to below 10^-3 monolayers are estimated. The capacity of the method is demonstrated for three catalytic reactions, CO and H₂ oxidation on Pt and NO_x conversion to N₂ on Pt/BaO.

More details from Chalmers University of Technology press release: New nanomethod paves the way for new measuring technology and hypersensitive sensors....

Abstract in Science: Nanoplasmonic Probes of Catalytic Reactions...

CleanSense...

The Physics arXiv Blog explains:

Angelani and co say there is in important difference between Brownian and bacterial motion: the former is in equilibrium but the latter is an open system with a net income of energy provided by nutrients. This breaks the time symmetry allowing energy to be extracted in the form of directed motion.

Now Angelani and co have built one these asymmetric and persuaded a bath full of E. Coli to push it round at a of 1rpm. Interestingly, Angelani and co report that most of the work is done by just a few bacteria, saying that only 2 out of 10 bacteria attached to a single tooth seem to be contributing to the torque.

In theory, they could speed up the rotation rate by persuading the others to put their backs into it. The linear motion of the gears is currently about 2 micrometres per second while the maximum speed of the bacteria is about 20 micrometers per second.

More at The Physics arXiv Blog...

Full article in arXiv: A bacterial ratchet motor

Nanowerk explains:

The delivery platform developed by Rozhkova [Elena Rozhkova from Argonne's NanoBio Interfaces group] and her colleagues uses 5 nm titanium dioxide nanoparticles that are covalently conjugated with an antibody that specifically targets certain tumors, including GBM. A naturally occurring metabolite of dopamin, DOPAC, is used as a linker molecule to tether the antibody to the nanoparticles. The whole thing works like this: the titanium dioxide/antibody nanobiocomposite binds exclusively to GBM cells. The hybrid semiconductor particles absorb energy from light, which is then transferred to molecular oxygen, producing cytotoxic reactive oxygen species (ROS). ROS damages the cell membrane and induces programmed death of the cancer cell.

More from Nanowerk: Nanotechnology therapy for brain cancer...

Abstract in Nano Letters: A High-Performance Nanobio Photocatalyst for Targeted Brain Cancer Therapy...

Flashback: Quantum Dots May Prove Effective Against Cancer Cells...

According to Nadeau [Jay Louise Nadeau, an Assistant Professor of Microbiology and Immunology at McGill --ed.] 'some nanoparticles don't make singlet oxygen but they do when they are connected to small molecules like [the neurotransmitter] dopamine. That opens up a whole other avenue for investigation,' she says. Her team also found that the dopamine-conjugated quantum dots can be used to kill mammalian cells but only on irradiation with UV-to-blue light. This means the quantum dots are unlikely to be toxic in the body, where the light cannot penetrate, but could have an effect on skin, the researchers claim. They suggest that similar conjugated nanoparticles could potentially be used in photodynamic therapy for skin cancer treatment.

Juan Mareque-Rivas, an expert in fluorescent nanoparticles, from the University of Edinburgh, UK, says 'this is a long overdue investigation. It is nice to see a study in which generation of different reactive oxygen species is demonstrated, quantified and rationalised, and linked to interactions with dopamine - it warns that biomolecules can enhance the phototoxicity of quantum dots.'

More from Chemistry World: Topical treatment for quantum dots?

Full article in Nanoscale...