Scientists create ‘evolved’ protein that may stop cancer from spreading

September 28, 2014

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A team of Stanford researchers has developed a protein therapy that disrupts the process that causes cancer cells to break away from original tumor sites, travel through the blood stream and start aggressive new growths elsewhere in the body.

This process, known as metastasis, can cause to spread with deadly effect.

“The majority of patients who succumb to cancer fall prey to metastatic forms of the disease,” said Jennifer Cochran, an associate professor of bioengineering who describes a new therapeutic approach in Nature Chemical Biology.

Today doctors try to slow or stop metastasis with chemotherapy, but these treatments are unfortunately not very effective and have severe side effects.

The Stanford team seeks to stop metastasis, without side effects, by preventing two proteins – Axl and Gas6 – from interacting to initiate the spread of cancer.

Axl proteins stand like bristles on the surface of cancer cells, poised to receive biochemical signals from Gas6 proteins.

When two Gas6 proteins link with two Axls, the signals that are generated enable cancer cells to leave the original tumor site, migrate to other parts of the body and form new cancer nodules.

To stop this process Cochran used protein engineering to create a harmless version of Axl that acts like a decoy. This decoy Axl latches on to Gas6 proteins in the blood stream and prevents them from linking with and activating the Axls present on .

In collaboration with Professor Amato Giaccia, who heads the Radiation Biology Program in Stanford’s Cancer Center, the researchers gave intravenous treatments of this bioengineered decoy protein to mice with aggressive breast and ovarian cancers.

Mice in the breast cancer treatment group had 78 percent fewer metastatic nodules than untreated mice. Mice with had a 90 percent reduction in metastatic nodules when treated with the engineered decoy protein.

“This is a very promising therapy that appears to be effective and non-toxic in pre-clinical experiments,” Giaccia said. “It could open up a new approach to cancer treatment.”

Giaccia and Cochran are scientific advisors to Ruga Corp., a biotech startup in Palo Alto that has licensed this technology from Stanford. Further preclinical and animal tests must be done before determining whether this therapy is safe and effective in humans.

Early but promising tests in lab mice suggest that a bioengineered ‘decoy’ protein, administered intravenously, can halt the spread of cancer from the original tumor site. Years of subsequent tests lie ahead. But this approach might one day provide …more

Greg Lemke, of the Molecular Neurobiology Laboratory at the Salk Institute, called this “a prime example of what bioengineering can do” to open up new therapeutic approaches to treat .

“One of the remarkable things about this work is the binding affinity of the decoy protein,” said Lemke, a noted authority on Axl and Gas6 who was not part of the Stanford experiments.

“The decoy attaches to Gas6 up to a hundredfold more effectively than the natural Axl,” Lemke said. “It really sops up Gas6 and takes it out of action.”

Directed Evolution

The Stanford approach is grounded on the fact that all biological processes are driven by the interaction of proteins, the molecules that fit together in lock-and-key fashion to perform all the tasks required for living things to function.

In nature proteins evolve over millions of years. But bioengineers have developed ways to accelerate the process of improving these tiny parts using technology called directed evolution. This particular application was the subject of the doctoral thesis of Mihalis Kariolis, a bioengineering graduate student in Cochran’s lab.

Using genetic manipulation, the Stanford team created millions of slightly different DNA sequences. Each DNA sequence coded for a different variant of Axl.

The researchers then used high-throughput screening to evaluate over 10 million Axl variants. Their goal was to find the variant that bound most tightly to Gas6.

Kariolis made other tweaks to enable the bioengineered decoy to remain in the bloodstream longer and also to tighten its grip on Gas6, rendering the decoy interaction virtually irreversible.

Yu Rebecca Miao, a postdoctoral scholar in Giaccia’s lab, designed the testing in animals and worked with Kariolis to administer the decoy Axl to the lab mice. They also did comparison tests to show that sopping up Gas6 resulted in far fewer secondary cancer nodules.

Irimpan Mathews, a protein crystallography expert at the SLAC National Accelerator Laboratory, joined the research effort to help the team better understand the binding mechanism between the Axl decoy and Gas6.

Protein crystallography captures the interaction of two proteins in a solid form, allowing researchers to take X-ray-like images of how the atoms in each protein bind together. These images showed molecular changes that allowed the bioengineered Axl decoy to bind Gas6 far more tightly than the natural Axl protein.

Next steps

Years of work lie ahead to determine whether this protein therapy can be approved to treat cancer in humans. Bioprocess engineers must first scale up production of the Axl decoy to generate pure material for clinical tests. Clinical researchers must then perform additional animal tests in order to win approval for and to conduct human trials. These are expensive and time-consuming steps.

But these early, hopeful results suggest that the Stanford approach could become a non-toxic way to fight metastatic cancer.

Glenn Dranoff, a professor of medicine at Harvard Medical School and a leading researcher at the Dana-Farber Cancer Institute, reviewed an advance copy of the Stanford paper but was otherwise unconnected with the research. “It is a beautiful piece of biochemistry and has some nuances that make it particularly exciting,” Dranoff said, noting that tumors often have more than one way to ensure their survival and propagation.

Axl has two protein cousins, Mer and Tyro3, that can also promote metastasis. Mer and Tyro3 are also activated by Gas6.

“So one therapeutic decoy might potentially affect all three related proteins that are critical in cancer development and progression,” Dranoff said.

Explore further: Scientists identify how immune cells use two critical receptors to clear dead cells from the body

More information: An engineered Axl ‘decoy receptor’ effectively silences the Gas6-Axl signaling axis, Nature Chemical Biology, DOI: 10.1038/nchembio.1636

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Interactive Bionic Man, featuring 14 novel biotechnologies

September 21, 2014

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The National Institute of Biomedical Imaging and Bioengineering has launched the “NIBIB Bionic Man,” an interactive Web tool that showcases cutting-edge research in biotechnology.

The bionic man features 14 technologies currently being developed by NIBIB-supported researchers.

Examples include a powered prosthetic leg that helps users achieve a more natural gait, a wireless brain-computer interface that lets people who are paralyzed control computer devices or robotic limbs using only their thoughts, and a micro-patch that delivers vaccines painlessly and doesn’t need refrigeration.

http://www.nibib.nih.gov/science-education/bionic-man

Artificial spleen cleans up blood

September 17, 2014

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A microfluidic cartridge from the Biomimetic Spleen device where pathogens are removed from contaminated blood

Researchers have developed a high-tech method to rid the body of infections — even those caused by unknown pathogens. A device inspired by the spleen can quickly clean blood of everything from Escherichia coli to Ebola, researchers report on 14 September in Nature Medicine1.

Blood infections can be very difficult to treat, and can lead to sepsis, an often-fatal immune response. More than 50% of the time, physicians cannot diagnose the cause of an infection that has prompted sepsis, and so they resort to antibiotics that attack a broad range of bacteria2. This approach is not always effective, and can lead to antibiotic resistance in bacteria.

In search of a way to clear any infection, a team led by Donald Ingber, a bioengineer at the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts, developed an artificial ‘biospleen’ to filter blood.

The device uses a modified version of mannose-binding lectin (MBL), a protein found in humans that binds to sugar molecules on the surfaces of more than 90 different bacteria, viruses and fungi, as well as to the toxins released by dead bacteria that trigger the immune overreaction in sepsis.

The researchers coated magnetic nanobeads with MBL. As blood enters the biospleen device, passes by the MBL-equipped nanobeads, which bind to most pathogens. A magnet on the biospleen device then pulls the beads and their quarry out of the blood, which can then be routed back into the patient.

Harvard’s Wyss Institute

The ‘biospleen’ uses protein-equipped nanobeads and a magnet to cleanse blood of pathogens.

Spleen screen

To test the device, Ingber and his team infected rats with either E. coli or Staphylococcus aureus and filtered blood from some of the animals through the biospleen. Five hours after infection, 89% of the rats whose blood had been filtered were still alive, compared with only 14% of those that were infected but not treated. The researchers found that the device had removed more than 90% of the bacteria from the rats’ blood. The rats whose blood had been filtered also had less inflammation in their lungs and other organs, suggesting they would be less prone to sepsis.

The researchers then tested whether the biospleen could handle the volume of blood in an average adult human — about 5 litres. They ran human blood containing a mixture of bacteria and fungi through the biospleen at a rate of 1 litre per hour, and found that the device removed most of the pathogens within five hours.

That degree of efficacy is probably enough to control an infection, Ingber says. Once the biospleen has removed most pathogens from the blood, antibiotics and the immune system can fight off remaining traces of infection — such as pathogens lodged in the organs, he says.

Ingber says that the biospleen could also help to treat viral diseases such as HIV and Ebola, in which survival depends on lowering the amount of virus in the blood to a negligible level. His group is now testing the biospleen on pigs.

Nigel Klein, an infection and immunity expert at University College London, says that the biospleen could also allow diagnosticians to collect samples of a pathogen from the blood and then culture it to identify it and determine what drugs will best treat it. As blood transfusion and filtration are already common practices, he expects that the biospleen could move into human clinical trials within a couple of years.

Nature
doi:10.1038/nature.2014.15917
http://www.nature.com/news/artificial-spleen-cleans-up-blood-1.15917
Video

MIT’s Robotic Cheetah Can Now Run And Jump While Untethered

September 15, 2014

Well, we knew it had to happen someday. A DARPA-funded robotic cheetah has been released into the wild, so to speak. A new algorithm developed by MIT researchers now allows their quadruped to run and jump — while untethered — across a field of grass.

The Pentagon, in an effort to investigate technologies that allow machines to traverse terrain in unique ways (well, at least that’s what they tell us), has been funding (via DARPA) the development of a robotic cheetah. Back in 2012, Boston Dynamics’ version smashed the landspeed record for the fastest mechanical mammal of Earth, reaching a top speed of 28.3 miles (45.5 km) per hour.

Researchers at MIT have their own version of robo-cheetah, and they’ve taken the concept in a new direction by imbuing it with the ability to run and bound while completely untethered.

MIT News reports:

The key to the bounding algorithm is in programming each of the robot’s legs to exert a certain amount of force in the split second during which it hits the ground, in order to maintain a given speed: In general, the faster the desired speed, the more force must be applied to propel the robot forward. Sangbae Kim, an associate professor of mechanical engineering at MIT, hypothesizes that this force-control approach to robotic running is similar, in principle, to the way world-class sprinters race.

“Many sprinters, like Usain Bolt, don’t cycle their legs really fast,” Kim says. “They actually increase their stride length by pushing downward harder and increasing their ground force, so they can fly more while keeping the same frequency.”

Kim says that by adapting a force-based approach, the cheetah-bot is able to handle rougher terrain, such as bounding across a grassy field. In treadmill experiments, the team found that the robot handled slight bumps in its path, maintaining its speed even as it ran over a foam obstacle.

“Most robots are sluggish and heavy, and thus they cannot control force in high-speed situations,” Kim says. “That’s what makes the MIT cheetah so special: You can actually control the force profile for a very short period of time, followed by a hefty impact with the ground, which makes it more stable, agile, and dynamic.”

This particular model, which weighs just as much as a real cheetah, can reach speeds of up to 10 mph (16 km/h) in the lab, even after clearing a 13-inch (33 cm) high hurdle. The MIT researchers estimate that their current version may eventually reach speeds of up to 30 mph (48 km/h).

It’s an impressive achievement, but Boston Dynamics’ WildCat is still the scariest free-running bot on the planet.

http://io9.com/mits-robotic-cheetah-can-now-run-and-jump-while-untethe-1634799433

Silicon Valley Investor Backs $1 Million Prize to End Death

September 14, 2014

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Based on the rapid rate of biomedical breakthroughs, we believe the question is not if we can crack the aging code, but when will it happen,” says Keith Powers, the producer of the prize group.

On Tuesday a group of doctors, investors, and researchers announced the Palo Alto Longevity Prize. The latest attempt to crack the code of life, it will award $1 million to teams of scientists that demonstrate a reversal of the aging process in test animals. About 10 teams have already signed up to compete for the prize, including researchers from nearby Stanford University, as well as the Texas Heart Institute in Houston and Washington University in St. Louis. “We spend more than $2 trillion per year on health care and do a pretty good job helping people live longer, but ultimately you still die,” says Dr. Joon Yun, a doctor, investor and the main backer of the prize. “The better plan is to end health care altogether.”

Mankind has spent centuries obsessing about ending aging for obvious reasons. Of late, Silicon Valley has emerged as one of the places most interested in the topic. Google (GOOG), for example, has created a biotech research house called Calico to develop therapies that may increase lifespans. It also employs Ray Kurzweil, who has proposed downloading one’s brain into a machine as a means of cheating death. And just last month, a Hyatt hotel in Silicon Valley played host to the Rejuvenation Biotechnology Conference at which top scientists discussed “emerging regenerative medicine solutions for the diseases of aging.”

In the case of the Palo Alto Longevity Prize, the antiaging focus will be studying and altering heart rate variability. HRV is the measure of the change in time from one heartbeat to the next. Instead of looking at a person’s average heart beat of, say, 60 beats per minute, HRV monitors performance at the next layer down, providing a better indicator of how a person is reacting to stress or injury. A $500,000 prize will go to a team that can take an older mammal and bring its HRV characteristics back to those of a young adult mammal; another $500,000 will go to a team that can extend an animal’s lifespan by 50 percent.

Participants will be able to review the rules and register to compete until January 15 of next year. A number of research groups were consulted about the effort ahead of its official announcement and have already signed on to have a go at winning the prize. Their approaches include experiments with stem cells, gene modification, and electrical stimulation, all aimed at tweaking HRV.

Yun, a radiologist by training, served on the clinical staff at Stanford Hospital. He’s also spent about 15 years working as an investor at Palo Alto Investors, a hedge fund with more than $1 billion in assets that has focused on health-care companies. The firm is known for making on average one large investment per year. One of its recent successes was InterMune, a biotech company thatRoche (ROG) just agreed to acquire for $8.3 billion in cash. Palo Alto Investors had put $200 million into the company.

According to Yun, the health-care system has not focused enough on restoring the body’s homeostatic capacity, its ability to operate at a healthy equilibrium. “Your intrinsic homeostasis erodes at 40,” he says. “Hangovers that used to last a day now last three days. Coughs drag on for months. You come off a roller coaster, and you feel awful, because you can’t self center and your blood vessels don’t recalibrate fast enough.” The goal with the prize would be to find a way to reverse these degrading processes and return the body to a more youthful state.

Yun says his father-in-law recently passed away at the age of 68, and this, combined with conversations with his friends, inspired him to tackle aging. “I come from an old school Korean farming family where you were just expected to till the farms and die,” he says. “There was something grand and dignified in that. But after my wife’s father died of something pretty preventable, I asked myself, ‘Why am I waiting to do something about this?’”

The idea to offer a prize came from Yun’s nanny, who is an acquaintance of Google’s Chairman Eric Schmidt and his wife Wendy. The Schmidts have sponsored, among other things, a $2 million prize to study the health of the ocean.

“Based on the rapid rate of biomedical breakthroughs, we believe the question is not if we can crack the aging code, but when will it happen,” says Keith Powers, the producer of the prize group. Yun has set aside a large chunk of money to fund not just this initial prize but subsequent attempts at solving the aging puzzle. “The prize is winnable, but I don’t think we will hit a grand slam on the first one,” he says. “I expect to be writing lots of checks.”

http://www.businessweek.com/articles/2014-09-09/silicon-valley-investor-backs-1-million-longevity-prize

Palo Alto Longevity Prize: http://paloaltoprize.com/

Japanese woman is first recipient of next-generation stem cells

September 14, 2014

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“We’ve taken a momentous first step toward regenerative medicine using iPS cells,” Takahashi said in a statement. “With this as a starting point, I definitely want to bring [iPS cell-based regenerative medicine] to as many people as possible.”

A Japanese woman in her 70s is the world’s first recipient of cells derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

In a two-hour procedure starting at 14:20 local time today, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimetre sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.

The procedure took place at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the epithelium sheets. She derived them from the patient’s skin cells, after producing induced pluripotent stem (iPS) cells and then getting them to differentiate into retinal cells.

Afterwards, the patient experienced no effusive bleeding or other serious problems, RIKEN has reported.

The patient “took on all the risk that go with the treatment as well as the surgery”, Kurimoto said in a statement released by RIKEN. “I have deep respect for bravery she showed in resolving to go through with it.”

He hit a somber note in thanking Yoshiki Sasai, a CDB researcher who recenty committed suicide. “This project could not have existed without the late Yoshiki Sasai’s research, which led the way to differentiating retinal tissue from stem cells.”

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at Kyoto University “without whose discovery of iPS cells, this clinical research would not be possible.” Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for that work.

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see ‘Next-generation stem cells cleared for human trial‘).

To earn that, Takahashi and her collaborators had done safety studies in both monkeys and mice. The animal tests found that iPS cells were not rejected and did not lead to the growth of tumours (see ‘Stem cells cruise to clinic‘).

Age-related macular degeneration results from the breakdown of retinal epithelium, a layer of cells that support photoreceptors needed for vision. The procedure Kurimoto performed is unlikely to restore his patient’s vision. However, researchers around the world will be watching closely to see whether the cells are able to check the further destruction of the retina while avoiding potential side-effects, such as bringing about an immune reaction or inducing cancerous growth.

“We’ve taken a momentous first step toward regenerative medicine using iPS cells,” Takahashi said in a statement. “With this as a starting point, I definitely want to bring [iPS cell-based regenerative medicine] to as many people as possible.”

http://www.nature.com/news/japanese-woman-is-first-recipient-of-next-generation-stem-cells-1.15915

Biologists delay the aging process by ‘remote control’

September 14, 2014

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UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.

Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low.

Increasing the amount of AMPK in fruit flies’ intestines increased their lifespans by about 30 percent — to roughly eight weeks from the typical six — and the flies stayed healthier longer as well.

The research, published Sept. 4 in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research.

“We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,” Walker said.

Walker said that the findings are important because extending the healthy life of humans would presumably require protecting many of the body’s organ systems from the ravages of aging — but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.

Humans have AMPK, but it is usually not activated at a high level, Walker said.

“Instead of studying the diseases of aging — Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes — one by one, we believe it may be possible to intervene in the aging process and delay the onset of many of these diseases,” said Walker, a member of UCLA’s Molecular Biology Institute. “We are not there yet, and it could, of course, take many years, but that is our goal and we think it is realistic.

“The ultimate aim of our research is to promote healthy aging in people.”

The fruit fly, Drosophila melanogaster, is a good model for studying aging in humans because scientists have identified all of the fruit fly’s genes and know how to switch individual genes on and off. The biologists studied approximately 100,000 of them over the course of the study.

Lead author Matthew Ulgherait, who conducted the research in Walker’s laboratory as a doctoral student, focused on a cellular process called autophagy, which enables cells to degrade and discard old, damaged cellular components. By getting rid of that “cellular garbage” before it damages cells, autophagy protects against aging, and AMPK has been shown previously to activate this process.

Ulgherait studied whether activating AMPK in the flies led to autophagy occurring at a greater rate than usual.

“A really interesting finding was when Matt activated AMPK in the nervous system, he saw evidence of increased levels of autophagy in not only the brain, but also in the intestine,” said Walker, a faculty member in the UCLA College. “And vice versa: Activating AMPK in the intestine produced increased levels of autophagy in the brain — and perhaps elsewhere, too.”

Many neurodegenerative diseases, including both Alzheimer’s and Parkinson’s, are associated with the accumulation of protein aggregates, a type of cellular garbage, in the brain, Walker noted.

“Matt moved beyond correlation and established causality,” he said. “He showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that he could bypass AMPK and directly target autophagy.”

Walker said that AMPK is thought to be a key target of metformin, a drug used to treat Type 2 diabetes, and that metformin activates AMPK.

The research was funded by the National Institutes of Health’s National Institute on Aging (grants R01 AG037514 and R01 AG040288). Ulgherait received funding support from a Ruth L. Kirschstein National Research Service Award (GM07185) and Eureka and Hyde fellowships from the UCLA department of integrative biology and physiology.

Co-authors of the research were Anil Rana, a postdoctoral scholar in Walker’s lab; Michael Rera, a former UCLA postdoctoral scholar in Walker’s lab; and Jacqueline Graniel, who participated in the research as a UCLA undergraduate.


Story Source:

The above story is based on materials provided by University of California – Los Angeles. The original article was written by Stuart Wolpert. Note: Materials may be edited for content and length.

Calico and AbbVie announce R&D collaboration

September 6, 2014

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Plan R&D facility in S.F. Bay Area, may co-invest up to $1.5 billion to tackle age-related diseases

Calico and drug company AbbVie announced today a novel R&D collaboration intended to “help the two companies discover, develop, and bring to market new therapies for patients with age-related diseases, including for neurodegeneration and cancer.”

Calico is the Google-backed life sciences company that is led by Arthur D. Levinson Ph.D. (former chairman and CEO of Genentech) and Hal V. Barron, M.D. (former Executive Vice President and Chief Medical Officer of Genentech). Abbvie is a global, research-based biopharmaceutical company.

Under the agreement, the companies will combine their complementary strengths to accelerate the availability of new therapies for age-related diseases. Calico will use its scientific expertise to establish a world-class research and development facility, with a focus on drug discovery and early drug development. AbbVie will provide scientific and clinical development support and its commercial expertise to bring new discoveries to market

Details of the Research Collaboration

  • AbbVie and Calico will each initially provide up to $250 million to fund the collaboration with the potential for both sides to contribute an additional $500 million
  • Calico will be responsible for research and early development during the first five years and continue to advance collaboration projects through Phase 2a for a ten year period
  • AbbVie will support Calico in its early R&D efforts and, following completion of Phase 2a studies, will have the option to manage late-stage development and commercial activities
  • Both parties will share costs and profits equally

Calico expects to begin filling critical positions immediately and plans to establish a substantial team of scientists and research staff in the San Francisco Bay Area

http://www.kurzweilai.net/calico-and-abbvie-announce-rd-collaboration?utm_source=KurzweilAI+Weekly+Newsletter&utm_campaign=f2b29ef114-UA-946742-1&utm_medium=email&utm_term=0_147a5a48c1-f2b29ef114-282129417

A multifunctional medical nanoparticle

September 6, 2014

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“These are amazingly useful particles,” noted co-first author Yuanpei Li, a research faculty member in the Lam laboratory. “As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy) — all proven ways to destroy tumors.”

Researchers at UC Davis Comprehensive Cancer Center and other institutions have created biocompatible multitasking nanoparticles that could be used as contrast agents to light up tumors for MRI and PET scans or deliver chemo and other therapies to destroy tumors. The study was published online in Nature Communications.

“These are amazingly useful particles,” noted co-first author Yuanpei Li, a research faculty member in the Lam laboratory. “As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors, apply light to make the nanoparticles release singlet oxygen (photodynamic therapy), or use a laser to heat them (photothermal therapy) — all proven ways to destroy tumors.”

Jessica Tucker, program director of Drug and Gene Delivery and Devices at the National Institute of Biomedical Imaging and Bioengineering, which is part of the National Institutes of Health, said the approach outlined in the study has the ability to combine both imaging and therapeutic applications in a single platform, which has been difficult to achieve, especially in an organic, and therefore biocompatible, vehicle.

“This is especially valuable in cancer treatment, where targeted treatment to tumor cells, and the reduction of lethal effects in normal cells, is so critical,” she added.

These are not the first nanoparticles for medical use, but they may be the most versatile. Other particles are good at some tasks but not others. Non-organic particles, such as quantum dots or gold-based materials, work well as diagnostic tools but have safety issues. Organic probes are biocompatible and can deliver drugs but lack imaging or phototherapy applications.

Design of a multifunctional nanoparticle

The nanoparticles are built on a porphyrin/cholic acid polymer and are simple to make. Porphyrins are common organic compounds. Cholic acid is produced by the liver. The basic nanoparticles are 21 nanometers wide (a nanometer is one-billionth of a meter).

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers. At 32 nanometers, CNPs are ideally sized to penetrate tumors, accumulating among cancer cells while sparing healthy tissue.

In the study, the team tested the nanoparticles, both in vitro and in vivo, for a wide range of tasks:

  • CNPs effectively transported anti-cancer drugs, such as doxorubicin. Even when kept in blood for many hours, CNPs only released small amounts of the drug; however, when exposed to light or agents such as glutathione, they readily released their payloads.
  • The ability to precisely control chemotherapy release inside tumors could greatly reduce toxicity. CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.
  • CNPs can be configured to respond to light, producing singlet oxygen, reactive molecules that destroy tumor cells. They can also generate heat when hit with laser light. Significantly, CNPs can perform either task when exposed to a single wavelength of light.
  • CNPs combine imaging and therapeutics, simultaneously delivering treatment and monitoring treatment efficacy. They readily chelate imaging agents and can remain in the body for long periods. In animal studies, CNPs congregated in tumors, making them easier to read on an MRI. Because CNPs accumulated in tumors, and not so much in normal tissue, they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans.
  • “These particles can also be used as optical probes for image-guided surgery,” said Kit Lam of the Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis. “In addition, they can be used as highly potent photosensitizing agents for intraoperative phototherapy.”

The Lam lab and its collaborators plan to pursue preclinical studies and, if all goes well, proceed to human trials.

This research was funded by the National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, the Department of Defense, the Prostate Cancer Foundation, the Veterans Administration, and the California Institute for Regenerative Medicine.


Abstract of Nature Communications paper

Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nanoconstruct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart ‘all-in-one’ nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumour detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumours. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumours for photothermal therapy (PTT), and light to singlet oxygen for photodynamic therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs or therapeutic radio-metals into tumours.

Direct brain-to-brain communication demonstrated in human subjects

September 6, 2014

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In a first-of-its-kind study, an international team of neuroscientists and robotics engineers have demonstrated the viability of direct brain-to-brain communication in humans. Recently published in PLOS ONE the highly novel findings describe the successful transmission of information via the internet between the intact scalps of two human subjects — located 5,000 miles apart.

“We wanted to find out if one could communicate directly between two people by reading out the brain activity from one person and injecting brain activity into the second person, and do so across great physical distances by leveraging existing communication pathways,” explains coauthor Alvaro Pascual-Leone, MD, PhD, Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center (BIDMC) and Professor of Neurology at Harvard Medical School. “One such pathway is, of course, the internet, so our question became, ‘Could we develop an experiment that would bypass the talking or typing part of internet and establish direct brain-to-brain communication between subjects located far away from each other in India and France?'”

It turned out the answer was “yes.”

In the neuroscientific equivalent of instant messaging, Pascual-Leone, together with Giulio Ruffini and Carles Grau leading a team of researchers from Starlab Barcelona, Spain, and Michel Berg, leading a team from Axilum Robotics, Strasbourg, France, successfully transmitted the words “hola” and “ciao” in a computer-mediated brain-to-brain transmission from a location in India to a location in France using internet-linked electroencephalogram (EEG) and robot-assisted and image-guided transcranial magnetic stimulation (TMS) technologies.

Previous studies on EEG-based brain-computer interaction (BCI) have typically made use of communication between a human brain and computer. In these studies, electrodes attached to a person’s scalp record electrical currents in the brain as a person realizes an action-thought, such as consciously thinking about moving the arm or leg. The computer then interprets that signal and translates it to a control output, such as a robot or wheelchair.

But, in this new study, the research team added a second human brain on the other end of the system. Four healthy participants, aged 28 to 50, participated in the study. One of the four subjects was assigned to the brain-computer interface (BCI) branch and was the sender of the words; the other three were assigned to the computer-brain interface (CBI) branch of the experiments and received the messages and had to understand them.

Using EEG, the research team first translated the greetings “hola” and “ciao” into binary code and then emailed the results from India to France. There a computer-brain interface transmitted the message to the receiver’s brain through noninvasive brain stimulation. The subjects experienced this as phosphenes, flashes of light in their peripheral vision. The light appeared in numerical sequences that enabled the receiver to decode the information in the message, and while the subjects did not report feeling anything, they did correctly receive the greetings.

A second similar experiment was conducted between individuals in Spain and France, with the end result a total error rate of just 15 percent, 11 percent on the decoding end and five percent on the initial coding side.

“By using advanced precision neuro-technologies including wireless EEG and robotized TMS, we were able to directly and noninvasively transmit a thought from one person to another, without them having to speak or write,” says Pascual-Leone. “This in itself is a remarkable step in human communication, but being able to do so across a distance of thousands of miles is a critically important proof-of-principle for the development of brain-to-brain communications. We believe these experiments represent an important first step in exploring the feasibility of complementing or bypassing traditional language-based or motor-based communication.”


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Carles Grau, Romuald Ginhoux, Alejandro Riera, Thanh Lam Nguyen, Hubert Chauvat, Michel Berg, Julià L. Amengual, Alvaro Pascual-Leone, Giulio Ruffini. Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies. PLoS ONE, 2014; 9 (8): e105225 DOI: 10.1371/journal.pone.0105225