Blood Cells Deliver Drugs To Kill Cancer

For the first time, WSU researchers have demonstrated a way to deliver a drug to a tumor by attaching it to a blood cell. The innovation could let doctors target tumors with anticancer drugs that might otherwise damage healthy tissues.

To develop the treatment, a team led by Zhenjia Wang, an assistant professor of pharmaceutical sciences, worked at the microscopic scale using a nanotherapeutic particle so small that 1,000 of them would fit across the width of a hair. By attaching a nanoscale particle to an infection-fighting white blood cell, the team showed they can get a drug past the armor of blood vessels that typically shield a tumor. This has been a major challenge in nanotechnology drug delivery.

Working with colleagues in Spokane and China, Wang implanted a tumor on the flank of a mouse commonly chosen as a model for human diseases. The tumor was exposed to near-infrared light, causing an inflammation that released proteins to attract white blood cells, called neutrophils, into the tumor. The researchers then injected the mouse with gold nanoparticles treated with antibodies that mediate the union of the nanoparticles and neutrophils. When the tumor was exposed to infrared light, the light’s interaction with the gold nanoparticles produced heat that killed the tumor cells, Wang said. In the future, therapists could attach an anticancer drug like doxorubicin to the nanoparticle. This could let them deliver the drug directly to the tumor and avoid damaging nearby tissues, Wang said.

We have developed a new approach to deliver therapeutics into tumors using the white blood cells of our body,” Wang said. “This will be applied to deliver many anticancer drugs, such as doxorubicin, and we hope that it could increase the efficacy of cancer therapies compared to other delivery systems.”

Wang and Chu’s colleagues on the research are postdoctoral researcher Dafeng Chu, Ph.D. student Xinyue Dong, Jingkai Gu of Jilin University and Jingkai Gu of the University of Macau.

The researchers reported on the technique in the latest issue of the journal Advanced Materials.

Source: https://news.wsu.edu/

Glucose Monitoring Strip

A research group from the Center for Nanoparticle Research within the Institute for Basic Science (IBS) in South Korea has developed a convenient and accurate sweat-based glucose monitoring and maintenance device. The research group has furthered its previous study* (Nat. Nanotech. 11, 566, 2016) to enhance the efficiency of the sweat collection and sensing & therapy process. This sweat-based system allows rapid glucose measurement incorporating small and sensitive sensors and also comes in a disposable strip sensor to the convenience of users. This accurate glucose analysis allows to prescribe a multistep and precisely controlled dosage of drug.

sweat monitoring stripOptical camera image of the disposable sweat monitoring strip (left). The disposable sweat analysis strip on human skin with perspiration (middle).The disposable strip-type sensors connected to a zero insertion force AQ50 (ZIF) connector (right).

The previous study reported a wearable graphene-based patch that allows diabetes monitoring and feedback therapy by using human sweat. The device’s pH and temperature monitoring functions enable systematic corrections of sweat glucose measurements.

The conventional treatment protocol causes a huge stress to diabetics since it requires painful and repetitive blood-withdrawal and insulin shots. Patients become reluctant to take the periodic tests and treatments, aggravating the diabetes symptoms and suffer severe diabetic complications. A recent alternative approach, sweat-based monitoring offers a painless blood glucose monitoring method, enabling more convenient control of blood glucose levels. However, many challenges still exist for the practical application of the existing system: tedious blood collection procedure; error-prone, enzyme-based glucose sensing that may lead to overtreatment of drugs, etc.

To address such issues, the research group presented an easy-to-use and multistage module to ensure an accurate glucose monitoring and therapy. To speed up the sweat collection, the researchers redevised the system to work under a small amount of sweat. They used electrochemically active, porous metal electrodes (replacing the graphene materials of the previous study) to enhance the sensitivity of the system. Also the porous structure allows to form strong linkage among enzymes, resulting in increased reliability of the sensors under mechanical friction and deformation.

Source: http://www.ibs.re.kr/

How To Improve Hair Treatment

In shampoo ads, hair always looks like a shiny, smooth surface. But for physicists peering into microscopes, the hair surface looks much more rugged, as it is made of saw-tooth, ratchet-like scales. In a new theoretical study published in EPJ E, Matthias Radtke and Roland Netz have demonstrated that massaging hair can help to apply drug treatmentencapsulated in nanoparticles trapped in the channels formed around individual hairs – to the hair roots. This is because the oscillatory movement of the massaging directs the way these particles are transported.

hair

This phenomenon was previously discovered in experiments on pork skin samples, which were conducted by Jürgen Lademann, dermatologist at the Charité clinic in Berlin, Germany, and his team. It is also relevant at the microscopic scale, in the transport on microtubules taking place in two directions between the cells within our bodies. By constrast, these findings could also help find ways of preventing harmful nanoparticles from being transported along hairs into the wrong places.

In their work, the authors created a model in which a nanoparticle moves between two asymmetric surfaces. Using standard models of random motion, they moved one surface in an oscillatory fashion relative to the other. They demonstrated by virtue of their corrugated surfaces that channels created between individual hairs and the surrounding skin lead to nanoparticles being sucked into hair follicles if the hair is massaged, thanks to a “ratchetmechanism.

Further, the authors determined optimal transport conditions for different surface structures by varying the driving frequency, particle size, and the amplitude of the corrugated surface. They found that the ratchet effect switches from a flashing to a pushing effect, when the oscillation switches from perpendicular to parallel to the resting surface, respectively. Radtke and Netz also found that nanoparticles’ speed and ability to diffuse are greatly enhanced by the parallel oscillatory motion.

Source: https://www.springer.com/

Damaged teeth can be regrown naturally

A way to naturally regrow damaged teeth has been discovered by scientists in a breakthrough that could significantly reduce the need for fillings. Researchers at King’s College London (KCL) found that a drug designed to treat Alzheimer’s disease was able to stimulate the tooth to create new dentine capable of filling in large cavitiesTeeth can already cope with small areas of damage using the same process, but when the holes become too large a dentist must insert artificial cements or the tooth will be lost.

dentistCLICK ON THE IMAGE TO ENJOY THE VIDEO

The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities, by providing both pulp protection and restoring dentine,” said Professor Paul Sharpe, lead author of a paper in the journal Scientific Reports.  “In addition, using a drug that has already been tested in clinical trials for Alzheimer’s disease provides a real opportunity to get this dental treatment quickly into clinics.”

If a tooth is damaged or infected, the soft inner pulp can become exposed, risking further infection. When this happens, a band of dentine, the hard material that makes up most of the tooth, will attempt to bridge the gap and seal off the pulp. But the researchers found that the natural repair mechanism could be boosted if the drug  Tideglusib was used. Previously it has been trialled as a treatment for various neurological disorders, including Alzheimer’s. It works by stimulating stem cells, which can turn into any type of tissue in the body, already present in the pulp to create new dentine.

The drug and a substance called glycogen synthase kinase were applied to the tooth on a biodegradable sponge made from collagen. As the sponge degraded, it was replaced by dentineleading to complete, natural repair”, according to a statement about the research issued by KCL.

Source: http://www.independent.co.uk/

Immunotherapy Could Eradicate A Third of All Cancers

In August 2015, former US President Jimmy Carter, then 91, announced he had cancer. The diagnosis was metastatic melanoma, and it had spread to his brain. He thought he had merely weeks to live. Just four months later, he made headlines again, revealing he had tested cancer-free. Before long, doctors said he no longer needed treatment. That remarkable turn came from a combination of a traditional therapy, radiation, and a new one, an immunotherapy drug called Keytruda, which was delivered intravenously once every three weeks. Keytruda had only been approved for about a year at that point.

Drug companies see potential for a new group of mega moneymakers. Investors and billionaires, like former New York Mayor Michael Bloomberg and Silicon Valley billionaire Sean Parker, have invested hundreds of millions into researching new treatments. New drugs such as Keytruda are a type of immunotherapy called checkpoint inhibitors. Most people have a type of protein that stops their immune systems from fighting the cancerous cells. Keytruda and similar drugs block those proteins. It’s like taking down a guard tower, allowing the body’s own immune system force to flood past a barrier, where it then gets to work killing and clearing away the cancer cellsCheckpoint inhibitors were first approved to treat melanoma but have since gone on to tackle lung cancer, bladder cancer, blood cancers, and other cancers.

Dan Chen, vice president and global head of cancer immunotherapy development at Genentech considers  checkpoint inhibitor Tecentriq to be the foundation of the company’s cancer immunotherapy program.

cancer-cells

This is a critical program for us. It allowed us to learn an enormous amount about cancer immunity,” like how the drugs work to inhibit the checkpoints, Chen said. Genentech points to patients like Bob Schoenbauer to show why the company is “investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer.”

Schoenbauer had been diagnosed with late-stage inoperable lung cancer in 2013. Soon after, Schoenbauer was connected with a clinical trial of Tecentriq out of Georgetown University. “Almost immediately, the cough was going away,” his wife, Frances, said. “It worked so fast, I couldn’t believe how good he was feeling.” Schoenbauer, who still gets Tecentriq every three weeks, is active and walks to the mall in his Maryland town every morning. He’s in remission.

Still there are some major caveats. First, not everyone is responding to the drugs — for advanced stages of melanoma, the number of people still alive after two years was about 35%, compared to 29.7% over the same time for those taking chemotherapy. And sometimes new checkpoint inhibitors under development fail key trials.

Source: http://uk.businessinsider.com/

Pain Relief Spot Identified In Brain

Scientists have identified for the first time the region in the brain responsible for the “placebo effect” in pain relief, when a fake treatment actually results in substantial reduction of pain, according to new research from Northwestern Medicine and the Rehabilitation Institute of Chicago (RIC).

placebo_brain

The yellow and red sections of this brain image shows the unique brain region — the mid frontal gyrus — which Northwestern scientists discovered is responsible for placebo response in pain relief

Pinpointing the sweet spot of the pain killing placebo effect could result in the design of more personalized medicine for the 100 million Americans with chronic pain. The fMRI technology developed for the study has the potential to usher in an era of individualized pain therapy by enabling targeted pain medication based on how an individual’s brain responds to a drug.

Given the enormous societal toll of chronic pain, being able to predict placebo responders in a chronic pain population could both help the design of personalized medicine and enhance the success of clinical trials,” said Marwan Baliki, research scientist at RIC and an assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.
The finding also will lead to more precise and accurate clinical trials for pain medications by eliminating individuals with high placebo response before trials.

The study was published Oct. 27, 2016, in PLOS Biology.

Source: https://news.northwestern.edu/

90 Minutes To Annihilate Early Stage Prostate Cancer

A prostate cancer patient undergoing a new photodynamic therapy that’s exciting specialists. Developed in Israel, treatment takes 90 minutes and involves no radiation or chemotherapy. It’s pain free and tests in Latin America showed an impressive clear-up rate and minimal side effects for early stage patients.

Prostate cancer

The patient may be cured, he may not be even cured of his disease but he may have a remedy for 20-30 years which is exactly what we need. Most of these patients are men the age of 60-70, not all of them healthy, and if you give them 10-20 years with good health and without side effects, which is the main thing, then we’ve done a great thing and we’ve done a revolution“, says Professor Jack Baniel, Chief Urologist at the Ramat Aviv Medical Center.

Israeli start-up Steba Research developed the therapy, in conjunction with Weizmann Insititute professors. It’s a focal therapy, which destroys tumours in the prostate while leaving the gland and most tissue intact. Using ultrasound, doctors insert conductors into the body, close to blood vessels feeding the tumour. Illuminating optic fibres are placed inside the conductors. A drug called Tookad that makes light toxic to living tissue is injected into the patient’s blood.

When doctors light up the optic fibres inside the patient, the cells touched by light die instantly. This patient is delighted with his treatment.  “So one day after the treatment I was back at home and three days later I was back at the office with regular life like before, and today after I got the new MRI I found out that my life is back again and everything is like before, no side affects, sexual life like before and I feel great“, comments Yaron Sfadia, patient.
The treatment has already been approved in Mexico. Phase III trials are currently taking place in New York and the developers are confident it won’t be long before the treatment becomes widespread. Future work to extend the same photodynamic principles to other types of cancers is possible.

Source: http://www.reuters.com/

How To Fight Against The Number One Killer Of Babies

Using nanoparticles to engineer a special drug, a team of researchers has demonstrated in mice a new way to both reduce preterm birth and avoid the risks of medication in pregnancy to unborn babies.

Jerrie S. Refuerzo, M.D., of the University of Texas Medical School at Houston (UTHealth) was frustrated with the limitations of existing tocolytic (anti-contraction or labor-repressant) medications such as indomethacin in treating women experiencing preterm labor. These drugs can cross the placental barrier and cause a heart defect or other problems in the fetus. Dr. Refuerzo and Monica Longo, M.D., Ph.D. (UT Health), in collaboration with colleagues from Houston Methodist Research Institute, Biana Godin, PharmD, Ph.D., bioengineered an innovative microscopic nanoparticle of indomethacin aimed at reaching the pregnant uterus but not crossing the placenta to the fetus. This targeted liposomal indomethacin, called LIPINDORA, was coated with an oxytocin receptor antagonist to make it bind to uterine tissue. LIPINDORA was given to near-term pregnant mice and the researchers found that the treated mice were significantly less likely than controls to have preterm uterine contractions or to deliver prematurely.

baby

These findings are exciting because we don’t currently have any medication that can reliably stop contractions or prevent preterm birth without also crossing the mom’s placenta and causing risks to babies,” explained Edward R. B. McCabe, M.D., Ph.D,, senior vice president and chief medical officer of the March of Dimes.

Preterm birth (birth before 37 weeks of pregnancy) is the number one killer of babies in the United States.

Source: http://www.eurekalert.org/

HIV New Treatment: Once per Year

Protease inhibitors are a class of antiviral drugs that are commonly used to treat HIV, the virus that causes AIDS. Scientists at the University of Nebraska Medical Center designed a new delivery system for these drugs that, when coupled with a drug developed at the University of Rochester School of Medicine and Dentistry, rid immune cells of HIV and kept the virus in check for long periods. The results appear in the journal Nanomedicine: Nanotechnology, Biology and Medicine.

While current HIV treatments involve pills that are taken daily, the new regimens’ long-lasting effects suggest that HIV treatment could be administered perhaps once or twice per year.

Nebraska researcher Howard E. Gendelman designed the investigational drug delivery system–a so-called “nanoformulated” protease inhibitor. The nanoformulation process takes a drug and makes it into a crystal, like an ice cube does to water.  Next, the crystal drug is placed into a fat and protein coat, similar to what is done in making a coated ice-cream bar.  The coating protects the drug from being degraded by the liver and removed by the kidney.

When tested together with URMC-099, a new drug discovered in the laboratory of UR scientist Harris A. (“Handy”) Gelbard M.D., Ph.D., the nanoformulated protease inhibitor completely eliminated measurable quantities of HIV. URMC-099 boosted the concentration of the nanoformulated drug in immune cells and slowed the rate at which it was eliminated, thereby prolonging its therapeutic effect.

HIV virus

The chemical marriage between URMC-099 and antiretroviral drug nanoformulations could increase drug longevity, improve patient compliance, and reduce general toxicities,” said Gendelman, lead study author and professor and chair of the Dept.  of Pharmacology and Neuroscience at Nebraska, who has collaborated with Gelbard for 24 years. “We are excited about pursing this research for the treatment and eradication of HIV infections.

Source: https://www.urmc.rochester.edu/

The Rise Of The NanoRobots

Nanomachines – including nano-sized motors, rockets and even cars – are many orders of magnitude smaller than a human cell, but they have huge promise. In the future, they could deliver drugs anywhere in the body, clean up oil spills and might even be used as artificial muscle cells. Find out more about these molecular machines (and the challenges that nanobot researchers still face) in Reactions’ latest video, produced in collaboration with the University of Nebraska‘s SciPop series.


nanorobots
CLICK ON THE IMAGE TO ENJOY THE VIDEO

Source: http://www.acs.org/

 

Liver Cancer: Hope Is Coming From Plants

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated death worldwide. Also called malignant hepatoma, HCC is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). These regrettably poor prognoses are due to the difficulty in treating this cancer using conventional chemotherapeutic drugs such as doxorubicin, epirubicin, cisplatin, 5-fluorouracil, etoposide or combinations therein. This may be attributed to that the conventional medicines are not able to reach in a sufficient concentration in the liver tumor cells at levels that are not harmful to the rest of the body.
thunder-god-vine

Now a team of scientists, led by Prof. Taeghwan Hyeon at the Institute for Basic Science (IBS)/Seoul National University and Prof. Kam Man Hui at the National Cancer Center Singapore, has screened a library containing hundreds of natural products against a panel of HCC cells to search a better drug candidate. The screen uncovered a compound named triptolide, a traditional Chinese medicine isolated from the thunder god vine (Tripterygium wilfordii (Latin) or lei gong teng (Chinese)) which was found to be far more potent than current therapies. Studies from other researchers corroborate the findings as triptolide has also found to be very effective against several other malignant cancers including; pancreatic, neuroblastoma and cholangiocarcinoma. However this excitement was tempered when the drug was administered to mice as the increased potency was coupled with increased toxicity as well. Prof. Hyeon et al. endeavoured to alleviate the toxic burden by increasing the specific delivery of the drug to the tumor using a nanoformulation. The designed formulation was a pH-sensitive nanogel coated with the nucleotide precursor, folate.
Source: http://www.ibs.re.kr/

Self-Assembled Nanofibers Mimic Living Cells Fibers

Researchers from Carnegie Mellon University have developed a novel method for creating self-assembled protein/polymer nanostructures that are reminiscent of fibers found in living cells. The work offers a promising new way to fabricate materials for drug delivery and tissue engineering applications.

nanofibersCarnegieMellon
The building blocks of the fibers are a few modified green fluorescent protein (GFP) molecules linked together using a process called click chemistry. An ordinary GFP molecule does not normally bind with other GFP molecules to form fibers.
We have demonstrated that, by adding flexible linkers to protein molecules, we can form completely new types of aggregates. These aggregates can act as a structural material to which you can attach different payloads, such as drugs. In nature, this protein isn’t close to being a structural material,” said Tomasz Kowalewski, professor of chemistry in Carnegie Mellon‘s Mellon College of Science.
But when Carnegie Mellon graduate student Saadyah Averick, working under the guidance of Krzysztof Matyjaszewski, Professor of Chemistry, modified the GFP molecules and attached PEO-dialkyne linkers to them, they noticed something strange — the GFP molecules appeared to self-assemble into long fibers. Importantly, the fibers disassembled after being exposed to sound waves, and then reassembled within a few days. Systems that exhibit this type of reversible fibrous self-assembly have been long sought by scientists for use in applications such as tissue engineering, drug delivery, nanoreactors and imaging.
This was purely curiosity-driven and serendipity-driven work,” Kowalewski said. “But where controlled polymerization and organic chemistry meet biology, interesting things can happen“.
The findings were published in the July 28 issue of Angewandte Chemie International Edition.
Source: http://www.cmu.edu/