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Nanotube therapy takes aim at breast cancer stem cells

WINSTON-SALEM, N.C. – Feb. 9, 2012 – Wake Forest Baptist Medical Center researchers have again proven that injecting multiwalled carbon nanotubes (MWCNTs) into tumors and heating them with a quick, 30-second laser treatment can kill them.

The results of the first effort involving kidney tumors was published in 2009, but now they've taken the science and directed it at breast cancer tumors, specifically the tumor initiating cancer stem cells. These stem cells are hard to kill because they don't divide very often and many anti-cancer strategies are directed at killing the cells that divide frequently.

The Wake Forest Baptist research findings are reported online ahead of April print publication in the journal Biomaterials. The research is a result of a collaborative effort between Wake Forest School of Medicine, the Wake Forest University Center for Nanotechnology and Molecular Materials, and Rice University. Lead investigator and professor of biochemistry Suzy V. Torti, Ph.D., of Wake Forest Baptist, said the breast cancer stem cells tend to be resistant to drugs and radiotherapy, so targeting these particular cells is of great interest in the scientific community.

"They are tough. These are cells that don't divide very often. They just sort of sit there, but when they receive some sort of trigger – and that's not really well understood – it's believed they can migrate to other sites and start a metastasis somewhere else," Torti explained. "Heat-based cancer treatments represent a promising approach for the clinical management of cancers, including breast cancer."

Link to the study.

A Single Cell Endoscope Berkeley Lab Researchers Use Nanophotonics for Optical Look Inside Living Cells

An endoscope that can provide high-resolution optical images of the interior of a single living cell, or precisely deliver genes, proteins, therapeutic drugs or other cargo without injuring or damaging the cell, has been developed by researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab). This highly versatile and mechanically robust nanowire-based optical probe can also be applied to biosensing and single-cell electrophysiology.

A team of researchers from Berkeley Lab and the University of California (UC) Berkeley attached a tin oxide nanowire waveguide to the tapered end of an optical fibre to create a novel endoscope system. Light travelling along the optical fibre can be effectively coupled into the nanowire where it is re-emitted into free space when it reaches the tip. The nanowire tip is extremely flexible due to its small size and high aspect ratio, yet can endure repeated bending and buckling so that it can be used multiple times.

Full story.

Carbon nanotube muscles generate giant twist for novel motors

Twist per muscle length is over a thousand times higher than for previous artificial muscles and the muscle diameter is ten times smaller than a human hair.

New artificial muscles that twist like the trunk of an elephant, but provide a thousand times higher rotation per length, were announced on Oct. 13 for a publication in Science magazine by a team of researchers from The University of Texas at Dallas, The University of Wollongong in Australia, The University of British Columbia in Canada, and Hanyang University in Korea.

These muscles, based on carbon nanotubes yarns, accelerate a 2000 times heavier paddle up to 590 revolutions per minute in 1.2 seconds, and then reverse this rotation when the applied voltage is changed. The demonstrated rotation of 250 per millimeter of muscle length is over a thousand times that of previous artificial muscles, which are based on ferroelectrics, shape memory alloys, or conducting organic polymers. The output power per yarn weight is comparable to that for large electric motors, and the weight-normalized performance of these conventional electric motors severely degrades when they are downsized to millimeter scale.

These muscles exploit strong, tough, highly flexible yarns of carbon nanotubes, which consist of nanoscale cylinders of carbon that are ten thousand times smaller in diameter than a human hair. Important for success, these nanotubes are spun into helical yarns, which means that they have left and right handed versions (like our hands), depending upon the direction of rotation during twisting the nanotubes to make yarn. Rotation is torsional, meaning that twist occurs in one direction until a limiting rotation results, and then rotation can be reversed by changing the applied voltage. Left and right hand yarns rotate in opposite directions when electrically charged, but in both cases the effect of charging is to partially untwist the yarn.

Unlike conventional motors, whose complexity makes them difficult to miniaturize, the torsional carbon nanotube muscles are simple to inexpensively construct in either very long or millimeter lengths. The nanotube torsional motors consist of a yarn electrode and a counter-electrode, which are immersed in an ionically conducting liquid. A low voltage battery can serve as the power source, which enables electrochemical charge and discharge of the yarn to provide torsional rotation in opposite directions. In the simplest case, the researchers attach a paddle to the nanotube yarn, which enables torsional rotation to do useful work – like mixing liquids on "micro-fluidic chips" used for chemical analysis and sensing.

The mechanism of torsional rotation is remarkable. Charging the nanotube yarns is like charging a supercapacitor - ions migrate into the yarns to electrostatically balance the electronic charge electrically injected onto the nanotubes. Although the yarns are porous, this influx of ions causes the yarn to increase volume, shrink in length by up to a percent, and torsionally rotate. This surprising shrinkage in yarn length as its volume increases is explained by the yarn's helical structure, which is similar in structure to finger cuff toys that trap a child's fingers when elongated, but frees them when shortened.

Nature has used torsional rotation based on helically wound muscles for hundreds of millions of years, and exploits this action for such tasks as twisting the trunks of elephants and octopus limbs. In these natural appendages, helically wound muscle fibers cause rotation by contracting against an essentially incompressible, bone-less core. On the other hand, the helically wound carbon nanotubes in the nanotube yarns are undergoing little change in length, but are instead causing the volume of liquid electrolyte within the porous yarn to increase during electrochemical charging, so that torsional rotation occurs.

The combination of mechanical simplicity, giant torsional rotations, high rotation rates, and micron-size yarn diameters are attractive for applications, such as microfluidic pumps, valve drives, and mixers. In a fluidic mixer demonstrated by the researchers, a 15 micron diameter yarn rotated a 200 times larger radius and 80 times heavier paddle in flowing liquids at up to one rotation per second.

"The discovery, characterization, and understanding of these high performance torsional motors shows the power of international collaborations", said Ray H. Baughman, a corresponding author of the author of the Science article and Robert A. Welch Professor of Chemistry and director of The University of Texas at Dallas Alan G. MacDiarmid NanoTech Institute. "Researchers from four universities in three different continents that were born in eight different countries made critically important contributions."

Researchers' quest for gold

Scientists study element as nanoparticle, effect on female reproductive tract

By Kelly Hogan of the Journal Sentinel

July 18, 2011

For University of Wisconsin-Milwaukee researchers studying the toxicity of gold nanoparticles - a minuscule material with potentially big biomedical applications - the road to a new medical advance may or may not be paved with gold.

These ultrafine metallic particles, which are 1/80,000th the diameter of a human hair, hold great promise for treating diseases as diverse as cancer, diabetes or AIDS, but scientists must prove that new ways to treat disease will do no harm.

Reinhold Hutz, a professor of biological sciences at UWM, and graduate student Jeremy Larson are investigating whether gold nanoparticles target and disrupt the female reproductive tract - the only research of its kind in the United States.

Gold nanoparticles range in size from 1 to 100 nanometers; a nanometer is about one-billionth the size of a yardstick. Noting the remarkable scale of nanoparticles, Larson put the particles in perspective: "If a nanoparticle were the size of a football, a virus would be the size of a person."

What distinguishes nanoparticles from particles of other sizes is their unique physical and chemical properties. The compatibility of other biological molecules with gold nanoparticles, for example, renders them prime candidates for tissue-specific drug delivery.

Full story.

Researchers inject nanofiber spheres carrying cells into wounds to grow tissue

ANN ARBOR, Mich.—For the first time, scientists have made star-shaped, biodegradable polymers that can self-assemble into hollow, nanofiber spheres, and when the spheres are injected with cells into wounds, these spheres biodegrade, but the cells live on to form new tissue.

Developing this nanofiber sphere as a cell carrier that simulates the natural growing environment of the cell is a very significant advance in tissue repair, says Peter Ma, professor at the University of Michigan School of Dentistry and lead author of a paper about the research scheduled for advanced online publication in Nature Materials. Co-authors are Xiaohua Liu and Xiaobing Jin.

Full story.

Virus-mimicking nanoparticles can stimulate long lasting immunity

Emory postdoctoral fellow Sudhir Pai Kasturi, PhD, created tiny particles studded with molecules thatturn on Toll‑like receptors. He worked with colleague Niren Murthy, PhD, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Vaccine scientists say their “Holy Grail” is to stimulate immunity that lasts for a lifetime. Live viral vaccines such as the smallpox or yellow fever vaccines provide immune protection that lasts several decades, but despite their success, scientists have remained in the dark as to how they induce such long lasting immunity.

Scientists at the Emory Vaccine Center have designed tiny nanoparticles that resemble viruses in size and immunological composition and that induce lifelong immunity in mice. They designed the particles to mimic the immune‑stimulating effects of one of the most successful vaccines ever developed – the yellow fever vaccine. The particles, made of biodegradable polymers, have components that activate two different parts of the innate immune system and can be used interchangeablywith material from many different bacteria or viruses.

The results are described in this week’s issue of Nature.

“These results address a long‑standing puzzle in vaccinology: how do successful vaccines induce longlasting immunity?” says senior author Bali Pulendran, PhD, Charles Howard Candler professor of pathology and laboratory medicine at Emory University School of Medicine and a researcher at Yerkes National Primate Research Center.

“These particles could provide an instant way to stretch scarce supplies when access to viral material is limited, such as pandemic flu or during an emerging infection. In addition, there are many diseases, such as HIV, malaria, tuberculosis and dengue, that still lack effective vaccines, where we anticipate that this type of immunity enhancer could play a role.”

One injection of the live viral yellow fever vaccine, developed in the 1930s by Nobel Prize winner Max Theiler, can protect against disease‑causing forms of the virus for decades. Pulendran and his colleagues have been investigating how humans respond to the yellow fever vaccine, in the hopes of imitating it.

Several years ago, they established that the yellow fever vaccine stimulated multiple Toll‑like receptors (TLRs) in the innate immune system. TLRs are present in insects as well as mammals, birds and fish. They are molecules expressed by cells that can sense bits of viruses, bacteria and parasites and can activate the immune system. Pulendran’s group demonstrated that the immune system sensed the yellow fever vaccine via multiple TLRs, and that this was required for the immunity induced by the vaccine.

“TLRs are like the sixth sense in our bodies, because they have an exquisite capacity to sense viruses and bacteria, and convey this information to stimulate the immune response,” Pulendran says. “We found that to get the best immune response, you need to hit more than one kind of Toll‑like receptor. Our aim was to create a synthetic particle that accomplishes this task.”

Emory postdoctoral fellow Sudhir Pai Kasturi, PhD, created tiny particles studded with molecules thatturn on Toll‑like receptors. He worked with colleague Niren Murthy, PhD, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

“We are very excited about building on this platform to design improved vaccines for existing and emerging infectious diseases” says Kasturi, the primary author working in Pulendran’s lab at the Emory Vaccine Center. One of the particles’ components is MPL (monophosphoryl lipid A), a component of bacterial cell walls, and the other is imiquimod, a chemical that mimics the effects of viral RNA. The particles are made of PLGA—poly(lactic acid)‑co‑(glycolic acid)—a synthetic polymer used for biodegradable grafts and sutures.

All three components are FDA‑approved for human use individually. For several decades, the only FDA‑approved vaccine additive was alum, until a cervical cancer vaccine containing MPL was approved in 2009. Because of immune system differences between mice and monkeys, the scientists replaced imiquimod with the related chemical resiquimod for monkey experiments.

In mice, the particles can stimulate production of antibodies to proteins from flu virus or anthrax bacteria several orders of magnitude more effectively than alum, the authors found. In addition, the immune cells persist in lymph nodes for at least 18months, almost the lifetime of a mouse. In experiments with monkeys, nanoparticles with viral protein could induce robust responses greater than five times the response induced by a dose of the same viral protein given by itself, without the nanoparticles.

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The research was supported by the National Institutes of Health and the Bill and Melinda Gates Foundation.

Reference: doi:10.1038/nature09737 S.P. Kasturi et al. Programming the magnitude and persistence of antibody responses with innateimmunity. Nature (2011).

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focusing on teaching, research, health care and public service.

Learn more about Emory’s health sciences: 
Blog: http://emoryhealthblog.com 
Twitter: @emoryhealthsci 
Web: http://emoryhealthsciences.org

 

Magical BEANs: New Nano-sized Particles Could Provide Mega-sized Data Storage

The ability of phase-change materials to readily and swiftly transition between different phases has made them valuable as a low-power source of non-volatile or “flash” memory and data storage. Now an entire new class of phase-change materials has been discovered by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley that could be applied to phase change random access memory (PCM) technologies and possibly optical data storage as well.  The new phase-change materials – nanocrystal alloys of a metal and semiconductor – are called “BEANs,” for binary eutectic-alloy nanostructures.

Full story.

Air Force Treating Wounds With Lasers and Nanotech

•By Katie Drummond •May 5, 2010

Forget stitches and old-school sutures. The Air Force is funding scientists who are using nano-technology and lasers to seal up wounds at a molecular level.

It might sound like Star Trek tech, but it’s actually the latest in a series of ambitious Pentagon efforts to create faster, more effective methods of treating war-zone injuries.

Full story.

Ultrasensitive imaging method uses gold-silver 'nanocages'

WEST LAFAYETTE, Ind. - New research findings suggest that an experimental ultrasensitive medical imaging technique that uses a pulsed laser and tiny metallic "nanocages" might enable both the early detection and treatment of disease.

The system works by shining near-infrared laser pulses through the skin to detect hollow nanocages and solid nanoparticles - made of an alloy of gold and silver - that are injected into the bloodstream.

Unlike previous approaches using tiny metallic nanorods and nanospheres, the new technique does not cause heat damage to tissue being imaged. Another advantage is that it does not produce a background "auto fluorescent" glow of surrounding tissues, which interferes with the imaging and reduces contrast and brightness, said Ji-Xin Cheng (pronounced Gee-Shin), an associate professor of biomedical engineering and chemistry at Purdue University.

Full story.

UCLA researchers create 'fly paper' to capture circulating cancer cells

New method may help improve diagnosis, prognosis and treatment monitoring

By Rachel Champeau November 18, 2009

Just as fly paper captures insects, an innovative new device with nano-sized features developed by researchers at UCLA is able to grab cancer cells in the blood that have broken off from a tumor. 

 

These cells, known as circulating tumor cells, or CTCs, can provide critical information for examining and diagnosing cancer metastasis, determining patient prognosis, and monitoring the effectiveness of therapies. 

 

Metastasis — the most common cause of cancer-related death in patients with solid tumors — is caused by marauding tumor cells that leave the primary tumor site and ride in the bloodstream to set up colonies in other parts of the body. 

 

The current gold standard for examining the disease status of tumors is an analysis of metastatic solid biopsy samples, but in the early stages of metastasis, it is often difficult to identify a biopsy site. By capturing CTCs, doctors can essentially perform a "liquid" biopsy, allowing for early detection and diagnosis, as well as improved treatment monitoring.

 

To date, several methods have been developed to track these cells, but the UCLA team's novel "fly paper" approach may be faster and cheaper than others — and it appears to capture far more CTCs.

Full story.