One benefit of this technology as reported in the letter is the flexibility of the cell culture medium. Current products available use a fixed chemical environment in their scaffolding to support three dimensional growth of cells. Because certain cell populations have specific metabolic requirements which must be met by the culture medium, the fixed chemical environment of existing 3-D culture techniques may preclude specific cell populations from being used. However, because this technology does not rely on a chemical environment, cell lines are not limited by the medium they grow in but rather the ability to take in the iron laced hydrogel.

The researchers state the potential applications of their work include “biotechnology, drug discovery, stem cell research, or regenerative medicine.” They go on to say, “Indeed, a potential long-term goal is the possibility of accomplishing the ‘engineering’ of normal tissues or complex organs.” The technology has been licensed to n3D Biosciences out of Houston, Texas.

M. D. Anderson press release: 3-D Cell Culture: Making Cells Feel Right at Home

Abstract in Nature Nanotechnology: Three-dimensional tissue culture based on magnetic cell levitation

Link: n3D Biosciences...

A tidbit from Nanowerk:

In their experiments, the Spanish team fabricated different batches of polysilicon chips and then chose the most suitable device type with lateral dimensions of 1.5-3μm and with a thickness of 0.5 μm to be placed inside living cells. Cells were taken from Dictyostelium discoideum and human HeLa cells.

To further demonstrate the versatility of the technique, they studied the integration of different materials in a single chip and their 3D nanostructuring capability by using other common microelectronics techniques such as FIB milling.

After inserting the chips into the live cells, the researchers made sure that the cells remained alive and healthy. They found that over 90% of the chip-containing containing HeLa cell population remained viable 7 days after lipofection.

Read on at Nanowerk: Future bio-nanotechnology will use computer chips inside living cells...

Abstract in Small: Intracellular Silicon Chips in Living Cells

In past research, the team has demonstrated that by treating the cantilever with different substances, they can tell what other substances are present. For example, E. coli antibodies attached to the cantilever can detect the presence of E. coli in water.

The researchers have perfected the oscillators' design, Ilic [Rob Ilic, research associate at the Cornell NanoScale Science and Technology Facility] said, by laying their device on top of a layer of silicon dioxide, all of which rest on a silicon substrate. A pad with holes connects pegs of silicon dioxide, lined up like telephone poles, which eventually end at the cantilever.

A laser beam, switched on at the far end from the cantilever, travels down the device and causes the oscillator to wobble. The frequency is then measured by shining another laser on the oscillator and noting patterns in the reflected light.

The "telephone poles" allow the energy to move efficiently across the device by preventing it from buckling or sagging. The design makes it easy to read the resonant frequency of the cantilever.

In this process, the researchers discovered that over short distances, the energy from the laser came in the form of heat, which quickly dissipates. But when the laser was parked hundreds of microns away from the cantilever, the energy came in the form of acoustical waves that traveled through the device, dissipated more slowly, and allowed them to make their device longer.

Image: The nanoelectromechanical oscillator with the cantilever on the far right. The inset is a tilted 3-D profile of the structure, which shows the silicon dioxide posts.

Abstract in Journal of Applied Physics: Theoretical and experimental investigation of optically driven nanoelectromechanical oscillators

Press release: Nanoelectromechanical oscillators could lead to detection of harmful molecules, bacteria ...

From an abstract in Journal of The American Chemical Society:

By properly conjugating gold nanoparticles with specific peptides, we were successful in selectively transporting them to the nuclei of cancer cells. Confocal microscopy images of DNA double-strand breaks showed that localization of gold nanoparticles at the nucleus of a cancer cell damages the DNA. Gold nanoparticle dark-field imaging of live cells in real time revealed that the nuclear targeting of gold nanoparticles specifically induces cytokinesis arrest in cancer cells, where binucleate cell formation occurs after mitosis takes place. Flow cytometry results indicated that the failure to complete cell division led to programmed cell death (apoptosis) in cancer cells. These results show that gold nanoparticles localized at the nuclei of cancer cells have important implications in understanding the interaction between nanomaterials and living systems.

Press release with video of a cell unsuccessfully trying to divide: Using Gold Nanoparticles to Hit Cancer Where It Hurts ...

Abstract in Journal of The American Chemical Society: Nuclear Targeting of Gold Nanoparticles in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis

Gold nanorods can be "lit up" at will. Lasers at particular wavelengths excite surface plasmons that absorb the energy and emit a heat signature that can be detected by a probe laser. Because plasmons are highly polarized along a nanorod's length, reading the signal while turning the polarization of the laser tells researchers precisely how the rod is oriented.

An electron microscope photo from the new paper shows nanorods about 75 nanometers long and 25 nanometers wide on a glass slide at 90-degree angles to each other. An adjacent photothermal image shows them as pixilated smudges. The smudges are strongest when the laser polarization aligns lengthwise with the nanorods, but they disappear when the laser polarization and rods are 90 degrees out of phase.

"With plasmonics, you always have two properties: absorption and scattering," Link said. "Depending on the size, one or the other dominates. What's unique is that it's now possible to do both on the same structure or do it individually -- so we can only measure absorption or only measure scattering."

Nanorods much smaller than 50 nanometers are not detectable by some scattering methods, Link said, but photothermal detection should work with metallic particles as small as five nanometers; this makes them useful for biological applications.

Image: The graph at left shows how nanorods photographed in an electron microscope at right appear and disappear, based on their orientation, when their photothermal signatures are detected with polarized lasers.

Nano imaging takes turn for the better ...

Abstract in PNAS: Plasmonic nanorod absorbers as orientation sensors

The short-lived bubbles are very bright and can be made smaller or larger by varying the power of the laser. Because they are visible under a microscope, nanobubbles can be used to either diagnose sick cells or to track the explosions that are destroying them.

In laboratory studies published last year, Dmitri Lapotko and colleagues at the Laboratory for Laser Cytotechnologies at the A.V. Lykov Heat and Mass Transfer Institute in Minsk, Belarus, applied nanobubbles to arterial plaque. They found that they could blast right through the deposits that block arteries.

In the current study, Lapotko and Rice colleague Jason Hafner, associate professor of physics and astronomy and of chemistry, tested the approach on leukemia cells and cells from head and neck cancers. They attached antibodies to the nanoparticles so they would target only the cancer cells, and they found the technique was effective at locating and killing the cancer cells.

Lapotko said the nanobubble technology could be used for "theranostics," a single process that combines diagnosis and therapy. In addition, because the cell-bursting nanobubbles also show up on microscopes in real time, Lapotko said the technique can be used for post-therapeutic assessment, or what physicians often refer to as "guidance."

Press release: Rice physicists kill cancer with 'nanobubbles'

More at Nanowerk: Plasmonic nanobubbles combine diagnosis and treatment in one theranostic method...

Abstract in Nanotechnology: Tunable plasmonic nanobubbles for cell theranostics

Image: Ajda Gregorcic

From the study abstract in Nanomedicine:

A majority of ovarian cancer metastases result from the shedding of malignant cells from the primary tumor into the abdominal cavity. Free-floating cancer cells in serous effusions of late-stage ovarian cancer patients may spread to internal organs making effective treatment extremely difficult. Selective removal of ovarian cancer cells from serous fluids may abate metastasis and improve long-term prognoses. We have previously shown that superparamagnetic nanoparticles conjugated to an ephrin-A1 mimetic peptide with a high affinity for the EphA2 receptor can be used to capture and remove cultured human ovarian cancer cells from the peritonea of experimental mice. Here we demonstrate the potential clinical utility of the methodology by in vitro capture and isolation of cancer cells from the ascites fluid of ovarian cancer patients.

Press release: Magnetic Nanoparticles Show Promise for Combating Human Cancer

Abstract in Nanomedicine: Selective removal of ovarian cancer cells from human ascites fluid using magnetic nanoparticles

Image: Nanoparticles, in brown, attach themselves to cancer cells, in violet, from the human abdominal cavity. Credit: Ken Scarberry/Georgia Tech

The statement from UC Berkley explains:

The tiny probes measure a few hundred nanometers in diameter — one-thousandth the width of a human hair, and one-hundredth the size of most cancer cells. The team’s insight was to combine different materials — roughened gold on one side, and smooth polystyrene on the other — onto a single probe...

The sensing side of the nanocoral relies upon a technique called surface-enhanced Raman spectroscopy (SERS), which takes advantage of the electromagnetic excitations that occur as molecules make contact with the roughened surface of a metal, such as gold. Molecules produce oscillations that resonate at signature frequencies when exposed to laser light, revealing their presence to the scientists.

The researchers verified the sensitivity of the nanocoral by measuring its ability to detect a standard chemical compound for Raman spectroscopy.

To get the nanocoral to target specific cells, the researchers took advantage of the capability to attach antibodies to polymer surfaces.

"We can tailor the nanocoral to cancer cells of interest by attaching the appropriate antibodies," said the study's other co-lead author, Liz Wu, who conducted this research as a Ph.D. student in the Applied Science and Technology program.

The researchers demonstrated this concept by coating the polystyrene surface with antibodies that attack human epidermal growth factor receptor 2 (HER-2), a well-known target for cancer treatment since it is often over-expressed in aggressive forms of breast cancer. They confirmed with both bright field and fluorescent images that the nanocoral attached to breast cancer cells with HER-2 receptors, while control experiments showed that no binding occurred when different antibodies or when cells lacking HER-2 were used.

Full story: Engineers develop cancer-targeting nanoprobe sensors...

Abstract in Small: Bioinspired Nanocorals with Decoupled Cellular Targeting and Sensing Functionality

Ho [Dean Ho, assistant professor of biomedical engineering and mechanical engineering] and Meade [Thomas J. Meade, professor in cancer research] imaged a variety of nanodiamond samples, including nanodiamonds decorated with various concentrations of Gd(III), undecorated nanodiamonds and water. The intense signal of the Gd(III)-nanodiamond complex was brightest when the Gd(III) level was highest.

"Nanodiamonds have been shown to be effective in attracting water molecules to their surface, which can enhance the relaxivity properties of the Gd(III)-nanodiamond complex," said Ho. "This might explain why these complexes are so bright and such good contrast agents."

"The nanodiamonds are utterly unique among nanoparticles," Meade said. "A nanodiamond is like a cargo ship -- it gives us a nontoxic platform upon which to put different types of drugs and imaging agents."

The biocompatibility of the Gd(III)-nanodiamond complex underscores its clinical relevance. In addition to confirming the improved signal produced by the hybrid, the researchers conducted toxicity studies using fibroblasts and HeLa cells as biological testbeds.

They found little impact of the hybrid complex on cellular viability, affirming the complex's inherent safety and positioning it as a clinically significant nanomaterial. (Other nanodiamond imaging methods, such as fluorescent nanodiamond agents, have limited tissue penetration and are more appropriate for histological applications.)

Nanodiamonds are carbon-based materials approximately four to six nanometers in diameter. Each nanodiamond's surface possesses carboxyl groups that allow a wide spectrum of compounds to be attached to it, not just gadolinium(III).

The researchers are exploring the pre-clinical application of the MRI contrast agent-nanodiamond hybrid in various animal models. With an eye towards optimizing this novel hybrid material, they also are continuing studies of the structure of the Gd(III)-nanodiamond complex to learn how it governs increased relaxivity.

Northwestern press release: Game-changing Nanodiamond Discovery for MRI...

Abstract in Nano Letters: Gd(III)-Nanodiamond Conjugates for MRI Contrast Enhancement

Flashbacks: Nanodiamonds Serve as Transport Mechanism for Therapeutic Insulin; NanoDiamonds...Everyone's Friend?; Nanofountain Delivers Therapeutic Particles Into Cells

Michael Berger over at Nanowerk reports:

The researchers' goal was to use the RNAi-based approach to specifically inhibit the PI3K/Akt signaling pathway – a key signal cascade for cancer cell proliferation and apoptosis – in brain tumor cells, which were surrounded by non-malignant cells, thus demonstrating the target specificity of a class of siRNA quantum dots (siRNA-QDs) that they developed.

In new work published by Lee's team and collaborators at UCLA ("Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum-Dot-Based siRNA Delivery"), the researchers first optimized their system by knocking down the expression of enhanced green fluorescent proteins (EGFP), and then using this optimized system they successfully suppressed the expression of EGFRvIII (epidermal growth factor receptor variant III) in the human GBM cell line, which subsequently led to cell apoptosis.

Read on at Nanowerk: Quantum dot based siRNA approach selectively inhibits brain cancer cells...

Abstract in Angewandte Chemie International Edition: Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum-Dot-Based siRNA Delivery

Image: Multifunctional siRNAQDs (red), when incubated in a co-culture of malignant tumor cells (U87-EGFP) and less tumorigenic cells (SK-N-BE(2)C), selectively transfected the U87 cells. Very few siRNA-QDs internalized within the less tumorigenic cells. (Scale bar = 50 µm).