How To Correct Genes That Cause High Cholesterol

U.S. researchers have used nanotechnology plus the powerful CRISPR-Cas9 gene-editing tool to turn off a key cholesterol-related gene in mouse liver cells, an advance that could lead to new ways to correct genes that cause high cholesterol and other liver diseasesNanotechnology is the design and manipulation of materials thousands of times smaller than the width of a human hair.

We’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” said study author Daniel Anderson, an associate professor in chemical engineering at the Massachusetts Institute of Technology.

The study, published  in Nature Biotechnology, holds promise for permanently editing genes such as PCSK9, a cholesterol-regulating gene that is already the target of two drugs made by the biotechnology companies Regeneron Pharmaceuticals and Amgen.

In the study, the scientists were trying to develop a safe and efficient way to deliver the components needed for CRISPR-Cas9, a type of molecular scissors that can selectively trim away defective genes and replace them with new stretches of DNA.

The system consists of a DNA-cutting enzyme called Cas9 and a stretch of RNA that guides the cutting enzyme to the correct spot in the genome. Most teams currently use viruses to deliver CRISPR into cells, an approach that is limited because the immune system can develop antibodies to viruses.

To overcome this, the team chemically modified the CRISPR components to protect them from enzymes in the body that would normally break them down. They then inserted this material into nano-scale fat particles and injected them into mice, where they made their way to liver cells.

In tests targeting the PCSK9 gene, the system proved highly effective, . The PCSK9 protein made by this gene was undetectable in the treated mice, eliminating the gene in more than 80 percent of liver cells, which also experienced a 35 percent drop in total cholesterol, the researchers reported.

High levels of cholesterol can clog arteries, causing reduced blood flow that can lead to a heart attack or stroke.

Source: http://news.mit.edu/

New Treatment To Kill Cancer

Raise your hand if you haven’t been touched by cancer,” says Mylisa Parette to a roomful of strangers. Parette, the research manager for Keystone Nano (KN), has occasional opportunities to present her company’s technologies to business groups and wants to emphasize the scope of the problem that still confronts society. “It’s easier to see the effects of cancer when nobody raises their hand,” she says. Despite 40 years of the War on Cancer, one in two men and one in three women will be diagnosed with the disease at some point in their lifetime. Parette and her Keystone Nano colleagues are working on a new approach to cancer treatment. The company was formed from the collaboration of two Penn State faculty members who realized that the nanoparticle research that the one was undertaking could be used to solve the drug delivery problems that the other was facing.

Mark Kester, a pharmacologist at Penn State College of Medicine in Hershey, was working with a new drug that showed real promise as a cancer therapy but that could be dangerous if injected directly into the bloodstream. Jim Adair, a materials scientist in University Park, was creating nontoxic nanoparticles that could enclose drugs that might normally be toxic or hydrophobic and were small enough to be taken up by cells.

The two combined their efforts and, licensing the resulting technology from Penn State, they joined with entrepreneur Jeff Davidson, founder of the Biotechnology Institute and the Pennsylvania Biotechnology Association, to form Keystone Nano. The new company’s first hire was Parette, whose job is to translate the lab-scale technology into something that can be ramped up to an industrial scale, and to prepare that technology for FDA approval leading to clinical trials.

Davidson, Parette, and KN’s research team work out of the Zetachron building, a long, one-story science incubator a mile from Penn State’s University Park campus. Operated by the Centre County Industrial Development Corporation, the building was originally the home of the successful Penn State spin-out company that gave it its name. A second Keystone Nano lab was recently opened in the Hershey Center for Applied Research, a biotech incubator adjacent to Penn State College of Medicine.

Our excitement is that we think our technology has shown efficacy in a whole range of animal models,” Davidson, Keystone CEO, remarks during a recent meeting in the shared conference room at Zetachron. “We understand the method of action, the active ingredient. We think it has every chance of being useful in treating disease. Our question is, how do we push this forward from where we are today to determining, one way or another, that it really does work?

Keystone Nano is pioneering two approaches to cancer therapy, both of which rely on advances in nanotechnology to infiltrate tumors and deliver a therapeutic agent. The approach nearest to clinical trials is a ceramide nanoliposome, or what Davidson calls a “nano fat ball around an active ingredient.” Kester, in whose lab the approach was developed, thinks of it as a basketball with a thick bilayer coating that contains 30 percent active ceramide and a hollow interior that can hold another cancer drug.

Source: http://news.psu.edu/

Dialysis Membrane Made From Graphene

Dialysis, in the most general sense, is the process by which molecules filter out of one solution, by diffusing through a membrane, into a more dilute solution. Outside of hemodialysis, which removes waste from blood, scientists use dialysis to purify drugs, remove residue from chemical solutions, and isolate molecules for medical diagnosis, typically by allowing the materials to pass through a porous membrane.

Today’s commercial dialysis membranes separate molecules slowly, in part due to their makeup: They are relatively thick, and the pores that tunnel through such dense membranes do so in winding paths, making it difficult for target molecules to quickly pass through.

Now MIT engineers have fabricated a functional dialysis membrane from a sheet of graphene — a single layer of carbon atoms, linked end to end in hexagonal configuration like that of chicken wire. The graphene membrane, about the size of a fingernail, is less than 1 nanometer thick. (The thinnest existing memranes are about 20 nanometers thick.) The team’s membrane is able to filter out nanometer-sized molecules from aqueous solutions up to 10 times faster than state-of-the-art membranes, with the graphene itself being up to 100 times faster.

While graphene has largely been explored for applications in electronics, Piran Kidambi, a postdoc in MIT’s Department of Mechanical Engineering, says the team’s findings demonstrate that graphene may improve membrane technology, particularly for lab-scale separation processes and potentially for hemodialysis.

Because graphene is so thin, diffusion across it will be extremely fast,” Kidambi says. “A molecule doesn’t have to do this tedious job of going through all these tortuous pores in a thick membrane before exiting the other side. Moving graphene into this regime of biological separation is very exciting.”

Kidambi is a lead author of a study reporting the technology, published today in Advanced Materials. Six co-authors are from MIT, including Rohit Karnik, associate professor of mechanical engineering, and Jing Kong, associate professor of electrical engineering.

Source: http://news.mit.edu/

Mental Viagra

As Valentines Day approaches, love may be in the air…. but it’s also in the mind. Scientists in London say a natural hormone – appropriately named kisspeptinenhances brain regions associated with sex and love. In placebo-controlled trials, 29 healthy young men were injected with kisspeptin and their brains scanned using MRI.

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During the MRI they performed tasks designed to activate certain areas of the brain. So we used tasks to activate the sexual arousal centres of the brain and task to activate the romance sensors of the brain using images. And we observed that kisspeptin boosted the activity in sexual arousal and romantic circuits in the brain,” says Dr. Alexander Comninos, Endocrinologist at Imperial College  London.

Kisspeptin is found in all men and women, and is vital for stimulating puberty. “So there’s a link, not just with the hormones, but also the stimulation of reproductive hormones but also stimulating how we perceive sexual images in the brain, and that’s what the really exciting part of this study been; is how for the first time having a link between a hormone that’s stimulating reproductive hormones, but also how our brains perceive sexual images,” explains Waljit Dhillo, Professor in Endocrinology at Imperial College London .

Psychological sexual disorders can make it difficult for couples to conceive. Biological factors play a large part, but the role of the brain and emotion can’t be overlooked. A kisspeptin-based therapy could be an answer, say researchers. It differs from drugs like Viagra, which only trigger a physiological response. “Viagra is very different. So Viagra will cause vasodilation, it will make the vessels essentially dilate, blood will go down to the genital area. So it’s a completely different action, it’s mechanical if you like. Whereas this is much more psychological in terms of its altering how we perceive sexual images in our brains. So it’s a completely different mechanism of action“, adds Professor Dhillo.

More research is needed – including on women and then eventually in patients with psychological issues. Kisspeptin could one day help treat sexual disorders of the mind… in effect, mental Viagra.

Source: http://www.reuters.com/

Paracetamol On Mars

How to produce medicine sustainably and cheaply, anywhere you want, whether in the middle of the jungle or even on Mars? Looking for a ‘mini-factory’ whereby sunlight can be captured to make chemical products? Inspired by the art of nature where leaves are able to collect enough sunlight to produce food, chemical engineers at Eindhoven University of Technology (TU/e) in Netherlands have presented such a scenario. 
Using sunlight to make chemical products has long been a dream of many a chemical engineer. The problem is that the available sunlight generates too little energy to kick off reactions. However, nature is able to do this. Antenna molecules in leaves capture energy from sunlight and collect it in the reaction centers of the leaf where enough solar energy is present for the chemical reactions that give the plant its food (photosynthesis).

Luminescent Solar Concentrator-based Photomicroreactor (LSC-PM, artificial leaf for organic synthesis), research by PhD Dario Cambie & Timothy Noël, group Micro Flow Chemistry and Process Technology, Chemical Engineering and Chemistry, TU Eindhoven. photo: TU/e, Bart van Overbeeke

Luminescent Solar Concentrator-based Photomicroreactor (LSC-PM, artificial leaf for organic synthesis), research by PhD Dario Cambie & Timothy Noël

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The researchers came across relatively new materials, known as luminescent solar concentrators (LSC’s), which are able to capture sunlight in a similar way. Special light-sensitive molecules in these materials capture a large amount of the incoming light that they then convert into a specific color that is conducted to the edges via light conductivity. These LSC’s are often used in practice in combination with solar cells to boost the yield.

 


The results surpassed all their expectations, and not only in the lab. “Even an experiment on a cloudy day demonstrated that the chemical production was 40 percent higher than in a similar experiment without LSC material”, says research leader Noël. “We still see plenty of possibilities for improvement. We now have a powerful tool at our disposal that enables the sustainable, sunlight-based production of valuable chemical products like drugs or crop protection agents.”

For the production of drugs there is certainly a lot of potential. The chemical reactions for producing drugs currently require toxic chemicals and a lot of energy in the form of fossil fuels. By using visible light the same reactions become sustainable, cheap and, in theory, countless times faster. But Noël believes it should not have to stop there. “Using a reactor like this means you can make drugs anywhere, in principle, whether malaria drugs in the jungle or paracetamol on Mars. All you need is sunlight and this mini-factory.

The findings are described in the journal Angewandte Chemie.

Source: https://www.tue.nl/

Nanoparticles And Immunotherapy, Allies To Eradicate Cancer

Some researchers are working to discover new, safer ways to deliver cancer-fighting drugs to tumors without damaging healthy cells. Others are finding ways to boost the body’s own immune system to attack cancer cells. Researchers at Pennsylvania State University   (Penn State) have combined the two approaches by taking biodegradable polymer nanoparticles encapsulated with cancer-fighting drugs and incorporating them into immune cells to create a smart, targeted system to attack cancers of specific types.

new-anti-cancer-drugs

The traditional way to deliver drugs to tumors is to put the drug inside some type of nanoparticle and inject those particles into the bloodstream,” said Jian Yang, professor of biomedical engineering, Penn State. “Because the particles are so small, if they happen to reach the tumor site they have a chance of penetrating through the blood vessel wall because the vasculature of tumors is usually leaky.”

The odds of interacting with cancer cells can be improved by coating the outside of the nanoparticles with antibodies or certain proteins or peptides that will lock onto the cancer cell when they make contact. However, this is still a passive drug delivery technology. If the particle does not go to the tumor, there is no chance for it to bind and deliver the drug.

Yang and Cheng Dong, professor of biomedical engineering, wanted a more active method of sending drugs to the cancer wherever it was located, whether circulating in the blood, the brain, or any of the other organs of the body.

“I have 10 years of working in immunology and cancer,” Dong said. “Jian is more a biomaterials scientist. He knows how to make the nanoparticles biodegradable. He knows how to modify the particles with surface chemistry, to decorate them with peptides or antibodies. His material is naturally fluorescent, so you can track the particles at the same time they are delivering the drug, a process called theranostics that combines therapy and diagnostics. On the other hand, I study the cancer microenvironment, and I have discovered that the microenvironment of the tumor generates kinds of inflammatory signals similar to what would happen if you had an infection.”

Immune cells, which were built to respond to inflammatory signals, will be naturally attracted to the tumor site. This makes immune cells a perfect active delivery system for Yang’s nanoparticles. The same technology is also likely to be effective for infectious or other diseases, as well as for tissue regeneration, Dong said.

Source: http://news.psu.edu/

Nanodrugs Help to cure 50 Rare Genetic Disorders

Researchers at Oregon State University and other institutions have discovered a type of drug delivery system that may offer new hope for patients with a rare, ultimately fatal genetic disorder – and make what might become a terrible choice a little easier.No treatment currently exists for this disease, known as Niemann Pick Type C1 disease, or NPC1, that affects about one in every 120,000 children globally, and results in abnormal cholesterol accumulation, progressive neurodegeneration and eventual death. However, a compound that shows promise is now undergoing clinical trials, but it has major drawbacks – the high doses necessary also cause significant hearing loss and lung damage, as well as requiring direct brain injection.

New findings, published today in Scientific Reports (“PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder”), outline the potential for a nanotechnology-based delivery system to carry the new drug into cells far more effectively, improve its efficacy by about five times, and allow use of much lower doses that may still help treat this condition without causing such severe hearing loss.The same system, they say, may ultimately show similar benefits for 50 or more other genetic disorders, especially those that require “brain targeting” of treatments.

X-linked_recessive._inheritance

Right now there’s nothing that can be done for patients with this disease, and the median survival time is 20 years,” said Gaurav Sahay, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and corresponding author on the new study. “The new cholesterol-scavenging drug proposed to treat this disorder, called cyclodextrin , may for the first time offer a real treatment. But it can cause significant hearing loss and requires multiple injections directly into the brain, which can be very traumatic. I’m very excited about the potential of our new drug delivery system to address these problems.”

Source: http://oregonstate.edu/

Smart Nanoparticles Fight Multidrug-resistant Cancer

Multidrug resistance (MDR) is the mechanism by which many cancers develop resistance to chemotherapy drugs, resulting in minimal cell death and the expansion of drug-resistant tumors. To address the problem of resistance, researchers have developed nanoparticles that simultaneously deliver chemotherapy drugs to tumors and inhibit the MDR proteins that pump the therapeutic drugs out of the cell. The process is known as chemosensitization, as blocking this resistance renders the tumor highly sensitive to the cancer-killing chemotherapy.

smart nanoparticlesMDR is a major factor in the failure of many chemotherapy drugs. The problem affects the treatment of a wide range of blood cancers and solid tumors, including breast, ovarian, lung, and colon cancers. Researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a part of the National Institutes of Health (NIH), are engineering multi-component nanoparticles that significantly enhance the killing of cancer cells.
Success in this medically important endeavor has required a team with a wide range of expertise to engineer nanoparticles that survive the journey to the tumor site, enter the tumor, and successfully perform the multiple functions for chemosensitization”, says Xiaoyuan Chen, Ph.D., who is the Senior Investigator, and has lead the work. His collaborators include scientists and engineers in China at Southeast University, Shenzhen University, Guangxi Medical University, and Shanghai Jiao Tong University, in addition to chemical engineers at the University of Leeds, United Kingdom.

The results of their experiments are reported in recent articles in Scientific Reports and Applied Materials & Interfaces.

Source: https://www.nibib.nih.gov/

Legions Of Nanorobots Attack Cancerous Cells

Researchers from Polytechnique Montréal, Université de Montréal and McGill University have just achieved a spectacular breakthrough in cancer research. They have developed new nanorobotic agents capable of navigating through the bloodstream to administer a drug with precision by specifically targeting the active cancerous cells of tumours. This way of injecting medication ensures the optimal targeting of a tumour and avoids jeopardizing the integrity of organs and surrounding healthy tissues. As a result, the drug dosage that is highly toxic for the human organism could be significantly reduced.

legions of nanorobots attack cancerous cells

These legions of nanorobotic agents were actually composed of more than 100 million flagellated bacteria – and therefore self-propelled – and loaded with drugs that moved by taking the most direct path between the drug’s injection point and the area of the body to cure,” explains Professor Sylvain Martel,  Director of the Polytechnique Montréal Nanorobotics Laboratory, who heads the research team’s work. “The drug’s propelling force was enough to travel efficiently and enter deep inside the tumours.”

When they enter a tumour, the nanorobotic agents can detect in a wholly autonomous fashion the oxygen-depleted tumour areas, known as hypoxic zones, and deliver the drug to them. This hypoxic zone is created by the substantial consumption of oxygen by rapidly proliferative tumour cells. Hypoxic zones are known to be resistant to most therapies, including radiotherapy.

But gaining access to tumours by taking paths as minute as a red blood cell and crossing complex physiological micro-environments does not come without challenges. So Professor Martel and his team used nanotechnology to do it.

 

This scientific breakthrough has just been published in the prestigious journal Nature Nanotechnology in an article titled “Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.” The article notes the results of the research done on mice, which were successfully administered nanorobotic agents into colorectal tumours.

Source: http://www.polymtl.ca/

Diabetes drug eliminates insulin injections

More than 400 million people around the world suffer from diabetes. Until recently it was thought that Type 2 diabetes was an adult onset condition. However, the WHO says it’s now occurring increasingly in children too. So news that Israeli drugmaker Oramed Pharmaceuticals Inc has developed an experimental oral insulin that safely reduces night-time blood glucose levels in type 2 patients is promising. Oramed‘s chief executive Nadav Kidron says the drug’s mid-stage trial shows there could be a healthier alternative to insulin injections.

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When you give it as an injection, it goes straight into the blood stream but when we give it orally, it goes first, it’s passed to the liver . . . and the liver is the organ that regulates the secretion of the insulin into the blood stream so that’s why it’s the healthier, more physiological way to treat diabetes through oral insulin“, Kidron says.

The study is surprising because until now many researchers thought insulin couldn’t survive the onslaught of digestive juices. Oramed says the new drug uses a protective coating and a high-enough dose of insulin so that most of it can be destroyed and still deliver a clinically beneficial amount of the hormone. The results must be replicated in a larger Phase III trial before the drug, known as ORMD-0801, can be submitted for approval.

Source: http://www.oramed.com/

How To Break The Brain Barrier To Kill Cancer

Using a laser probe, neurosurgeons at Washington University School of Medicine in St. Louis have opened the brain’s protective cover, enabling them to deliver chemotherapy drugs to patients with a form of deadly brain cancer. In a pilot study, 14 patients with glioblastoma – the most common and aggressive type of brain cancer – underwent minimally invasive laser surgery to treat a recurrence of their tumors. Heat from the laser is known to kill brain tumor cells but, unexpectedly, the researchers found that the technology can penetrate the blood-brain barrier.

laser breaks brain barrierCLICK ON THE IMAGE TO ENJOY THE VIDEO

The laser treatment kept the blood-brain barrier open for four to six weeks, providing us with a therapeutic window of opportunity to deliver chemotherapy drugs to the patients,” said co-corresponding author Eric C. Leuthardt, MD, a Washington University professor of neurosurgery who treats patients at Barnes-Jewish Hospital. “This is crucial because most chemotherapy drugs can’t get past the protective barrier, greatly limiting treatment options for patients with brain tumors. We are closely following patients in the trial,” said Leuthardt, who also is a Siteman Cancer Center member. “Our early results indicate that the patients are doing much better on average, in terms of survival and clinical outcomes, than what we would expect. We are encouraged but very cautious because additional patients need to be evaluated before we can draw firm conclusions.

The study is published online Feb. 24 in the journal PLOS ONE.

Source: https://medicine.wustl.edu/

Nanoparticle-Based Cancer Therapies Shown to Work in Humans

A team of researchers led by Caltech scientists has shown that nanoparticles can function to target tumors while avoiding adjacent healthy tissue in human cancer patients.

nanoparticle against brain cancer

Our work shows that this specificity, as previously demonstrated in preclinical animal studies, can in fact occur in humans“, says study leader Mark E. Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech. “The ability to target tumors is one of the primary reasons for using nanoparticles as therapeutics to treat solid tumors.
The scientists demonstrate that nanoparticle-based therapies can act as a “precision medicine” for targeting tumors while leaving healthy tissue intact. In the study, Davis and his colleagues examined gastric tumors from nine human patients both before and after infusion with a drug—camptothecin—that was chemically bound to nanoparticles about 30 nanometers in size.

Our nanoparticles are so small that if one were to increase the size to that of a soccer ball, the increase in size would be on the same order as going from a soccer ball to the planet Earth,” says Davis, who is also a member of the City of Hope Comprehensive Cancer Center in Duarte, California, where the clinical trial was conducted.

The team found that 24 to 48 hours after the nanoparticles were administered, they had localized in the tumor tissues and released their drug cargo, and the drug had had the intended biological effects of inhibiting two proteins that are involved in the progression of the cancer. Equally important, both the nanoparticles and the drug were absent from healthy tissue adjacent to the tumors.

The findings, have been published online in the journal Proceedings of the National Academy of Sciences.

Source: https://www.caltech.edu/