‘Drug Factory’ Implants Could Eliminate Specific Lung Cancer

Rice University and Baylor College of Medicine researchers have shown they can seradicate advanced-stage mesothelioma tumor in mice in just a few days with a treatment combining Rice’s cytokinedrug factoryimplants and a checkpoint inhibitor drug.

The researchers administered the drug-producing beads, which are no larger than the head of a pin, next to tumors where they could produce continuous, high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer. The study, published online today in Clinical Cancer Research, is the latest in a string of successes for the drug-factory technology invented in the lab of Rice bioengineer Omid Veiseh, including Food and Drug Administration (FDAapproval to begin clinical trials of the technology this fall in ovarian cancer patients.

From the beginning, our objective was to develop a platform therapy that can be used for multiple different types of immune system disorders or different types of cancers,” said Rice graduate student Amanda Nash, who spent several years developing the implant technology with study co-lead author Samira Aghlara-Fotovat, a fellow student in Veiseh’s lab.

The cytokine factories consist of alginate beads loaded with tens of thousands of cells that are genetically engineered to produce natural IL-2, one of two cytokines the FDA has approved for treatment of cancer. The factories are just 1.5 millimeters wide and can be implanted with minimally invasive surgery to deliver high doses of IL-2 directly to tumors. In the mesothelioma study, the beads were placed beside tumors and inside the thin layer of tissue known as the pleura, which covers the lungs and lines the interior wall of the chest.

I take care of patients who have malignant pleural mesothelioma,” said Dr. Bryan Burt, professor and chief of Baylor’s Division of Thoracic Surgery in the Michael E. DeBakey Department of Surgery. “This is a very aggressive malignancy of the lining of the lungs. And it’s very hard to treat completely by surgical resection. In other words, there is often residual disease that is left behind. The treatment of this residual disease with local immunotherapy — the local delivery of relatively high doses of immunotherapy to that pleural space — is a very attractive way to treat this disease.”

Veiseh said the mesothelioma study began when Burt and Baylor surgeon and associate professor Dr. Ravi Ghanta heard about the early results of ovarian cancer animal tests Veiseh’s team was conducting with collaborators at the University of Texas MD Anderson Cancer Center. In March, Veiseh and MD Anderson collaborators published a study showing IL-2-producing beads could eradicate advanced-stage ovarian and colorectal tumors in mice in less than a week.

They were really impressed by the preclinical data we had in ovarian cancer,” Veiseh said of Burt and Ghanta. “And they asked the question, ‘Could we actually leverage the same system for mesothelioma?’

Source: https://blogs.bcm.edu/

How to Block Pain

Researchers have published the first proof-of-concept results from a years-long program to develop tiny, wireless devices that can treat neurological diseases or block pain. The nerve stimulators require no batteries and instead draw both their power and programming from a low-powered magnetic transmitter outside the body.
The MagnetoElectric Bio ImplanT—aka ME-BIT—is placed surgically and an electrode is fed into a blood vessel toward the nerve targeted for stimulation. Once there, the device can be powered and securely controlled with a near-field transmitter worn close to the body. Researchers successfully tested the technology on animal models and found it could charge and communicate with implants several centimeters below the skin.
The implant, detailed in Nature Biomedical Engineering, could replace more invasive units that now treat Parkinson’s disease, epilepsy, chronic pain, hearing loss, and paralysis.

Because the devices are so small, we can use blood vessels as a highway system to reach targets that are difficult to get to with traditional surgery,” says Jacob Robinson, an associate professor of electrical and computer engineering and of bioengineering at Rice University. “We’re delivering them using the same catheters you would use for an endovascular procedure, but we would leave the device outside the vessel and place a guidewire into the bloodstream as the stimulating electrode, which could be held in place with a stent.”

The ability to power the implants with magnetoelectric materials eliminates the need for electrical leads through the skin and other tissues. Leads like those often used for pacemakers can cause inflammation, and sometimes need to be replaced. Battery-powered implants can also require additional surgery to replace batteries.

ME-BIT’s wearable charger requires no surgery. The researchers showed it could even be misaligned by several inches and still sufficiently power and communicate with the implant.

The programmable, 0.8-square-millimeter implant incorporates a strip of magnetoelectric film that converts magnetic energy to electrical power. An on-board capacitor can store some of that power, and a “system-on-a-chipmicroprocessor translates modulations in the magnetic field into data. The components are held together by a 3D-printed capsule and further encased in epoxy. The magnetic field generated by the transmitter—about 1 milliTesla—is easily tolerated by tissues, the researchers say. They estimate the current implant can generate a maximum of 4 milliwatts of power, sufficient for many neural stimulation applications.

One of the nice things is that all the nerves in our bodies require oxygen and nutrients, so that means there’s a blood vessel within a few hundred microns of all the nerves,” Robinson says. “It’s just a matter of tracing the right blood vessels to reach the targets. “With a combination of imaging and anatomy, we can be pretty confident about where we place the electrodes,” he says.

Source: https://www.futurity.org/

‘Drug Factory’ Implants Could Eliminate Cancer

Rice University bioengineers have shown they can eradicate advanced-stage ovarian and colorectal cancer in mice in as little as six days with a treatment that could be ready for human clinical trials later this year. The researchers used implantabledrug factories” the size of a pinhead to deliver continuous, high doses of interleukin-2, a natural compound that activates white blood cells to fight cancer. The drug-producing beads can be implanted with minimally invasive surgery. Each contains cells engineered to produce interleukin-2 that are encased in a protective shell.

The treatment and animal test results are described online today in a Science Advances study co-authored by Omid VeisehAmanda Nash and colleagues from Rice, the University of Texas MD Anderson Cancer Center, the University of Virginia and others.

Veiseh, an assistant professor of bioengineering whose lab produced the treatment, said human clinical trials could begin as soon as this fall because one of his team’s key design criteria was helping cancer patients as quickly as possible. The team chose only components that had previously proven safe for use in humans, and it has demonstrated the safety of the new treatment in multiple tests.

Rice University bioengineers Amanda Nash (left) and Omid Veiseh with vials of bead-like “drug factories” they created to treat cancer. The beads are designed to continuously produce natural compounds that program the immune system to attack tumors. 

We just administer once, but the drug factories keep making the dose every day, where it’s needed until the cancer is eliminated,” Veiseh said. “Once we determined the correct dose — how many factories we needed — we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer.”

In the newly published study, researchers placed drug-producing beads beside tumors and within the peritoneum, a sac-like lining that supports intestines, ovaries and other abdominal organs. Placement within this cavity concentrated interleukin-2 within tumors and limited exposure elsewhere. “A major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” said study co-author Dr. Amir Jazaeri, professor of gynecologic oncology and reproductive medicine at MD Anderson. “In this study, we demonstrated that the ‘drug factories’ allow regulatable local administration of interleukin-2 and eradication of tumor in several mouse models, which is very exciting. This provides a strong rationale for clinical testing.

Source: https://news.rice.edu/

Smart Clothing

There’s no need to don uncomfortable smartwatches or chest straps to monitor your heart if your comfy shirt can do a better job. That’s the idea behind “smart clothing” developed by a Rice University lab, which employed its conductive nanotube thread to weave functionality into regular apparel.

The Brown School of Engineering lab of chemical and biomolecular engineer Matteo Pasquali reported in the American Chemical Society journal Nano Letters that it sewed nanotube fibers into athletic wear to monitor the heart rate and take a continual electrocardiogram (EKG) of the wearer. The fibers are just as conductive as metal wires, but washable, comfortable and far less likely to break when a body is in motion, according to the researchers. On the whole, the shirt they enhanced was better at gathering data than a standard chest-strap monitor taking live measurements during experiments. When matched with commercial medical electrode monitors, the carbon nanotube shirt gave slightly better EKGs.

Rice University graduate student Lauren Taylor shows a shirt with carbon nanotube thread that provides constant monitoring of the wearer’s heart

The shirt has to be snug against the chest,” said Rice graduate student Lauren Taylor, lead author of the study. “In future studies, we will focus on using denser patches of carbon nanotube threads so there’s more surface area to contact the skin.”

Source: https://news.rice.edu/

How To Fine-Tune Bacterial Metabolism To Boost Longevity

Studies have shown that gut microbes can influence several aspects of the host’s life, including aging. Given the complexity and heterogeneity of the human gut environment, elucidating how a specific microbial species contributes to longevity has been challenging.

To explore the influence of bacterial products on the aging process, scientists at Baylor College of Medicine and Rice University developed a method that uses light to directly control gene expression and metabolite production from bacteria residing in the gut of the laboratory worm Caenorhabditis elegans.

The team reports (“Optogenetic control of gut bacterial metabolism to promote longevity”) in eLife that green-light-induced production of colanic acid by resident Escherichia coli bacteria protected gut cells against stress-induced cellular damage and extended the worm’s lifespan. The researchers indicate that this method can be applied to study other bacteria and propose that it also might provide in the future a new way to fine-tune bacterial metabolism in the host gut to deliver health benefits with minimal side effects.

Illustration of bacteria in the intestine.

Gut microbial metabolism is associated with host longevity. However, because it requires direct manipulation of microbial metabolism in situ, establishing a causal link between these two processes remains challenging. We demonstrate an optogenetic method to control gene expression and metabolite production from bacteria residing in the host gut. We genetically engineer an E. coli strain that secretes colanic acid (CA) under the quantitative control of light,” the investigators wrote.

Using this optogenetically-controlled strain to induce CA production directly in the C. elegans gut, we reveal the local effect of CA in protecting intestinal mitochondria from stress-induced hyper-fragmentation. We also demonstrate that the lifespan-extending effect of this strain is positively correlated with the intensity of green light, indicating a dose-dependent CA benefit on the host.

“Thus, optogenetics can be used to achieve quantitative and temporal control of [the microbiome] metabolism in order to reveal its local and systemic effects on host health and aging. “We used optogenetics, a method that combines light and genetically engineered light-sensitive proteins to regulate molecular events in a targeted manner in living cells or organisms,” said co-corresponding author Meng Wang, PhD, professor of molecular and human genetics at the Huffington Center on Aging at Baylor.

Source: https://www.genengnews.com/

Artificial Leaf Could Become A Source Of Perpetual Energy

Rice University researchers have created an efficient, low-cost device that splits water to produce hydrogen fuel. The platform developed by the Brown School of Engineering lab of Rice materials scientist Jun Lou integrates catalytic electrodes and perovskite solar cells that, when triggered by sunlight, produce electricity. The current flows to the catalysts that turn water into hydrogen and oxygen, with a sunlight-to-hydrogen efficiency as high as 6.7%. This sort of catalysis isn’t new, but the lab packaged a perovskite layer and the electrodes into a single module that, when dropped into water and placed in sunlight, produces hydrogen with no further input. The platform introduced by Lou, lead author and Rice postdoctoral fellow Jia Liang and their colleagues in the American Chemical Society journal ACS Nano is a self-sustaining producer of fuel that, they say, should be simple to produce in bulk.

A schematic and electron microscope cross-section show the structure of an integrated, solar-powered catalyst to split water into hydrogen fuel and oxygen. The module developed at Rice University can be immersed into water directly to produce fuel when exposed to sunlight

The concept is broadly similar to an artificial leaf,” Lou said. “What we have is an integrated module that turns sunlight into electricity that drives an electrochemical reaction. It utilizes water and sunlight to get chemical fuels.”

Perovskites are crystals with cubelike lattices that are known to harvest light. The most efficient perovskite solar cells produced so far achieve an efficiency above 25%, but the materials are expensive and tend to be stressed by light, humidity and heat.  “Jia has replaced the more expensive components, like platinum, in perovskite solar cells with alternatives like carbon,” Lou commented. “That lowers the entry barrier for commercial adoption. Integrated devices like this are promising because they create a system that is sustainable. This does not require any external power to keep the module running.”

Liang said the key component may not be the perovskite but the polymer that encapsulates it, protecting the module and allowing to be immersed for long periods. “Others have developed catalytic systems that connect the solar cell outside the water to immersed electrodes with a wire,” he explained. “We simplify the system by encapsulating the perovskite layer with a Surlyn (polymer) film.”

The patterned film allows sunlight to reach the solar cell while protecting it and serves as an insulator between the cells and the electrodes, Liang said. “With a clever system design, you can potentially make a self-sustaining loop,” Lou added. “Even when there’s no sunlight, you can use stored energy in the form of chemical fuel. You can put the hydrogen and oxygen products in separate tanks and incorporate another module like a fuel cell to turn those fuels back into electricity.”

Source: https://news.rice.edu/

Deadly ‘SuperBugs’ Destroyed by Molecular Drills

Molecular drills have gained the ability to target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics. In some cases, the drills make the antibiotics effective once again.

Researchers at Rice University, Texas A&M University, Biola University and Durham (U.K.) University showed that motorized molecules developed in the Rice lab of chemist James Tour are effective at killing antibiotic-resistant microbes within minutes.

These superbugs could kill 10 million people a year by 2050, way overtaking cancer,” Tour said. “These are nightmare bacteria; they don’t respond to anything.”

The motors target the bacteria and, once activated with light, burrow through their exteriors.

While bacteria can evolve to resist antibiotics by locking the antibiotics out, the bacteria have no defense against molecular drills. Antibiotics able to get through openings made by the drills are once again lethal to the bacteria.

Tour and Robert Pal, a Royal Society University Research Fellow at Durham and co-author of the new paper, introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that can be prompted to spin at 3 million rotations per second when activated with light.

Tests by the Texas A&M lab of lead scientist Jeffrey Cirillo and former Rice researcher Richard Gunasekera, now at Biola, effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.

Bacteria don’t just have a lipid bilayer,” Tour said. “They have two bilayers and proteins with sugars that interlink them, so things don’t normally get through these very robust cell walls. That’s why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect.”

The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance. “Sometimes, when the bacteria figures out a drug, it doesn’t let it in,” Tour said. “Other times, bacteria defeat the drug by letting it in and deactivating it.

He said meropenem is an example of the former. “Now we can get it through the cell wall,” Tour said. “This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills.”

The researchers reported their results in the American Chemical Society journal ACS Nano.

Source: https://news.rice.edu/

Bacteria trapped — and terminated — by graphene filter

Airborne bacteria may see what looks like a comfy shag carpet on which to settle. But it’s a trapRice University scientists have transformed their laser-induced graphene (LIG) into self-sterilizing filters that grab pathogens out of the air and kill them with small pulses of electricity. The flexible filter developed by the Rice lab of chemist James Tour may be of special interest to hospitalsAccording to the Centers for Disease Control and Prevention, patients have a 1-in-31 chance of acquiring a potentially antibiotic-resistant infection during hospitalization. The device described in the American Chemical Society journal ACS Nano captures bacteria, fungi, fungi, prions, endotoxins and other biological contaminants carried by droplets, aerosols and particulate matter. The filter then prevents the microbes and other contaminants from proliferating by periodically heating up to 350 degrees Celsius (662 degrees Fahrenheit), enough to obliterate pathogens and their toxic byproducts. The filter requires little power, and heats and cools within seconds.

LIG is a conductive foam of pure, atomically thin carbon sheets synthesized through heating the surface of a common polyimide sheet with an industrial laser cutter. The process discovered by Tour’s lab in 2014 has led to a range of applications for electronics, triboelectric nanogenerators, composites, electrocatalysis and even art. Like all pure graphene, the foam conducts electricity. When electrified, Joule heating raises the filter’s temperature above 300 C, enough to not only kill trapped pathogens but also to decompose toxic byproducts that can feed new microorganisms and activate the human immune system. The researchers suggested a single, custom-fit LIG filter could be efficient enough to replace the two filter beds currently required by federal standards for hospital ventilation systems.

Seen in an electron microscope image, micron-scale sheets of graphene created at Rice University form a two-layer air filter that traps pathogens and then kills them with a modest burst of electricity

So many patients become infected by bacteria and their metabolic products, which for example can result in sepsis while in the hospital,” Tour said. “We need more methods to combat the airborne transfer of not just bacteria but also their downstream products, which can cause severe reactions among patients.

“Some of these products, like endotoxins, need to be exposed to temperatures of 300 degrees Celsius in order to deactivate them,” a purpose served by the LIG filter, he added. “This could significantly lessen the transfer of bacteria-generated molecules between patients, and thereby lower the ultimate costs of patient stays and lessen sickness and death from these pathogens.”

The lab tested LIG filters with a commercial vacuum filtration system, pulling air through at a rate of 10 liters per minute for 90 hours, and found that Joule heating successfully sanitized the filters of all pathogens and byproducts. Incubating used filters for an additional 130 hours revealed no subsequent bacterial growth on the heated units, unlike control LIG filters that had not been heated.

Bacteria culturing experiments performed on a membrane downstream from the LIG filter indicated that bacteria are unable to permeate the LIG filter,” said Rice sophomore John Li, co-lead author of the paper with postdoctoral researcher Michael Stanford. Stanford noted the sterilization feature “may reduce the frequency with which LIG filters would need to be replaced in comparison to traditional filters.” Tour suggested LIG air filters could also find their way into commercial aircraft.

Source: https://news.rice.edu/

Flexible Generators Turn Movement Into Energy

Wearable devices that harvest energy from movement are not a new idea, but a material created at Rice University may make them more practical. The Rice lab of chemist James Tour has adapted laser-induced graphene (LIG) into small, metal-free devices that generate electricity. Like rubbing a balloon on hair, putting LIG composites in contact with other surfaces produces static electricity that can be used to power devices. For that, thank the triboelectric effect, by which materials gather a charge through contact. When they are put together and then pulled apart, surface charges build up that can be m.

In experiments, the researchers connected a folded strip of LIG to a string of light-emitting diodes and found that tapping the strip produced enough energy to make them flash. A larger piece of LIG embedded within a flip-flop let a wearer generate energy with every step, as the graphene composite’s repeated contact with skin produced a current to charge a small capacitor.

An electron microscope image shows a cross-section of a laser-induced graphene and polyimide composite created at Rice University for use as a triboelectric nanogenerator. The devices are able to turn movement into energy that can then be stored for later use

This could be a way to recharge small devices just by using the excess energy of heel strikes during walking, or swinging arm movements against the torso,” Tour said.

LIG is a graphene foam produced when chemicals are heated on the surface of a polymer or other material with a laser, leaving only interconnected flakes of two-dimensional carbon. The lab first made LIG on common polyimide, but extended the technique to plants, food, treated paper and wood.

The project is detailed in the American Chemical Society journal ACS Nano.

Source: http://news.rice.edu/

Nanotubes Boost Batteries Efficiency

The Rice lab of chemist James Tour showed thin nanotube films effectively stop dendrites that grow naturally from unprotected lithium metal anodes in batteries. Over time, these tentacle-like dendrites can pierce the battery’s electrolyte core and reach the cathode, causing the battery to fail. That problem has both dampened the use of lithium-metal  in commercial applications and encouraged researchers worldwide to solve it.

Lithium metal charges much faster and holds about 10 times more energy by volume than the lithium-ion electrodes found in just about every electronic device, including cellphones and electric cars.

Microscope images of lithium metal anodes after 500 charge/discharge cycles in tests at Rice University show the growth of dendrites is quenched in the anode at left, protected by a film of carbon nanotubes. The unprotected lithium metal anode at right shows evidence of dendrite growth

One of the ways to slow dendrites in lithium-ion batteries is to limit how fast they charge,” Tour said. “People don’t like that. They want to be able to charge their batteries quickly.”

The Rice team’s answer, detailed in Advanced Materials, is simple, inexpensive and highly effective at stopping dendrite growth, Tour said. “What we’ve done turns out to be really easy,” he said. “You just coat a lithium metal foil with a multiwalled carbon nanotube film. The lithium dopes the nanotube film, which turns from black to red, and the film in turn diffuses the lithium ions.

Source: http://news.rice.edu/