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An ionic forcefield for nanoparticles

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Nanoparticles may have the solution to awful side effects from chemotherapy. If doctors can use nanoparticles to carry drugs directly to a specific part of the body, they can make chemotherapautics less toxic.

But it is not that simple. Because nanoparticles trigger the body’s immune system to fight against them, the vast majority of them never reach their target.

Human blood serum contains proteins that tag the nanoparticles as invadors and a paltry 1% of the nanoparticles get to where they are going.

“No one escapes the wrath of the serum proteins,” said Eden Tanner, who was a postdoctoral Bioengeneering fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

A research team led by Tanner and Professor Samir Mitragotri have created an ionic forcefield that could enable nanoparticles to achieve their goal by preventing the proteins in the blood serum from tagging the nanoparticles.

In experimenting with mice, the researchers found that the could make the nanoparticles to survive longer in the human body using a coat of the ionic liquid. This coating increased the number of nanoparticles that reached their target from 1% to more than 50%.

“The fact that this coating allows the nanoparticles to slip past serum proteins and hitch a ride on red blood cells is really quite amazing because once you are able to fight the immune system effectively, lots of opportunities open up,” explained Mitragotri, who is part of the Harvard’s Wyss Institute for Biologically Inspired Engineering faculty.

Ionic liquids are liquid salts and they are capable of holding charge.

“We knew that serum proteins clear out nanoparticles in the bloodstream by attaching to the surface of the particle and we knew that certain ionic liquids can either stabilize or destabilize proteins,” said Tanner, an assistant professor of chemistry and biochemistry at the University of Mississippi. “The question was, could we leverage the properties of ionic liquids to allow nanoparticles to slip past proteins unseen.”

The great thing about ionic liquids is that every small change you make to their chemistry results in a big change in their properties,” explained Christine Hamadani, who was the first author and a former graduate student at SEAS. “By changing one carbon bond, you can change whether or not it attracts or repels proteins.”

At the moment, Hamadani is a graduate student based at Tanner’s lab in the University of Mississippi.

Researchers used choline hexenoate to coat the nanoparticles. It is an ionic liquid with a natural aversion to serum proteins. The nanoparticles coated with ionic liquid attached themselves to red-blood cells and remained in circulation until they got to the lungs.

“This hitchhiking phenomenon was a really unexpected discovery,” said Mitragotri. “Previous methods of hitchhiking required special treatment for the nanoparticles to attach to red blood cells and even then, they only stayed at a target location for about six hours. Here, we showed 50 percent of the injected dose still in the lungs after 24 hours.”

The scientists are yet to understand exactly why the nanoparticles so easily attached themselves to lung tissue, but it shows that the system can work with a fair amount of precision.

“This is such a modular technology,” said Tanner, who plans will go on with her research at University of Mississippi. “Any nanoparticle with a surface change can be coated with ionic liquids and there are millions of ionic liquids that can be tuned to have different properties. You could tune the nanoparticle and the liquid to target specific locations in the body.”

“We as a field need as many tools as we can to fight the immune system and get drugs where they need to go,” said Mitragotri. “Ionic liquids are the latest tool on that front.”

Morgan J. Goetz co-authored the research paper.

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Four-Week Memory Test that could predict the Risk of Alzheimer’s

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Scientists now believe that it may be possible to identify people who have a greater risk of developing Alzheimer’s disease by testing their memory over a four-week period.

Trials have shown that zeroing in on the ability to retain a memory over a longer period could yield potentially more accurate predictors than the traditional memory tests. Traditional memory tests assess people’s memory over a period of half an hour.

University of Bristol researchers led the study which they published in the Alzheimer’s Research and Therapy journal in which they wanted to test using a word list to test people’s memory over four weeks. People were tested for their memory of the list four weeks after hearing it initially.

Those whose memory of the list after four weeks was better off, registered less cognitive decline over the year after. This was true even for those who did not have any problems with cognitive function or memory at the start.

Forty six older people participated in the study. All of them were healthy and their average age was 70.7. The study participants had to perform three memory tasks. Researchers tested t heir delayed recall 30 minutes later and then four weeks later.

They also did the Addenbrooke’s Cognitive Examination III or ACE-III test. ACE-III test is conventionally used to detect cognitive impairments, as well as a brain MRI. One year later, the participants repeated the same ACE-III test to measure their cognitive abilities.

At the end of the study, researchers found that 15 out of 46 participants had experienced a decline in their cognitive abilities, and that the verbal memory tests conducted over the initial period of four weeks would have yielded a better prediction of this decline than the standard memory tests.

After combining the scores from the four-week memory tests together with the results of the MRI brain scan, the researchers found that it was possible to make even more accurate prediction s of cognitive decline.

The MRI brain scans showed that there was a size reduction in the section of the brain that governs memory. This is the part of the brain that gets affected by Alzheimer’s Disease.

By testing long-term memory recall, the researchers found that they could detect Alzheimer’s disease much earlier and achieve better treatment outcomes. Treatments to stop Alzheimer’s disease or slow down its progression are much more effective when given during the early stages of the disease. This is the best time because patients are yet to develop significant problems with their memory.

In the words of Dr. Alfie Wearn, a Research Associate at the Bristol Medical School: Translational Health Sciences: “Our study shows evidence for a low-cost and quick to administer screening tool that could be used to identify the very earliest signs of Alzheimer’s disease. It could also directly speed up the development of effective Alzheimer’s disease therapies, and enable earlier treatment when such therapies are available.”

Dr. Liz Coulthard who is an Associate Professor in Dementia Neurology with the University of Bristol as well as a neurologist with the North Bristol NHS Trust also said this: “It is important to note the participants were healthy older people who did not develop Alzheimer’s during the trial, but some people did show the type of change over the course of a year in memory and thinking that can precede Alzheimer’s disease. Future work will establish whether this test predicts full-blown Alzheimer’s dementia.”

Researchers will now be testing the ability of these tests to detect Alzheimer’s disease in comparison with other cognitive deteriorating diseases. The researchers will be drawing comparisons between long-term memory test results of people who have evidence of Alzheimer’s disease and those without. The evidence is derived from analyzing their cerebrospinal fluid. Even though this method of detecting Alzheimer’s is the most effective, it is also too invasive, and researchers are working on less invasive methods.

The study was conducted with funding from a Wellcome Trust PhD study scholarship award received by Dr. Wearn who is in the Neural Dynamics PhD Programme. It was also funded by the Alzheimer’s Research UK as well as Brace, which is a dementia charity at Southmead Hospital in Bristol.

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Nanodiamonds enhance paper-based diagnostic testing

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A study conducted by the University College London has shown that we can detect viruses earlier by exploiting nanodiamonds’ quantum properties to make paper-based diagnostic testing more sensitive.

The innovation could pave the way for viruses like SARS-CoV-2 and HIV to be detected earlier.

Paper-based diagnostic testing works the same way pregnancy tests work, by soaking a strip of paper in a liquid and waiting for a fluorescent signal or a color transformation to denote positive results, or the presence of virus proteins.

England is already piloting lateral flow testing for Covid-19 which deliver immediate results as they do not require laboratory processing. Lateral flow testing is popular for detecting viruses like HIV.

HIV tests lateral flow tests utilize gold nanoparticles which are not as sensitive as nanodiamonds which are capable of detecting much lower viral loads than gold nanoparticles. If this is widely accepted, it will become possible to detect viruses much earlier and reduce the risk of transmission.

“Our proof-of-concept study shows how quantum technologies can be used to detect ultralow levels of virus in a patient sample, enabling much earlier diagnosis,” explained Professor Rachel McKendry, lead author of the Nature study. “We have focused on the detection of HIV, but our approach is very flexible and can be easily adapted to other diseases and biomarker types.

“We are working on adapting our approach to Covid-19. We believe that this transformative new technology will benefit patients and protect populations from infectious diseases.”

The study leveraged the quantum properties of nanodiamonds that carried a defect which creates a nitrogen-vacancy center (NV). These NV centers can be used for fluorescent biomarking which enables ultrasensitive imaging, quantum computing, information processing, and other applications.

The NV centers emit fluorescent lights which indicate the presence of target molecules. Nano diamonds’ quantum properties allow this signal to be set to its own unique frequency that separates it from background fluorescence.

What the UCL research has shown is that it is possible to improve the sensitivity of a HIV test by 100,000 times. A 10-minte temperature amplification which multiplies HIV RNA copies made it possible to detect HIV in a single molecule within the sample.

“Paper-based lateral flow tests with gold nanoparticles do not require laboratory analysis, making them particularly useful in low-resource settings and where access to healthcare is limited. They are low cost, portable, and user friendly” said lead author Dr. Ben Miller.

He added: “However, these tests currently lack the sensitivity to detect very low levels of biomarkers. By replacing commonly used gold nanoparticles with fluorescent nanodiamonds in this new design, and selectively modulating their (already bright) emission of light, we have been able to separate their signal from the unwanted background fluorescence of the test strip, dramatically improving sensitivity.”

The researchers have now moved on to trying to adjust the same technology to develop a rapid testing for other diseases, including Covid-19. If they can create a hand-held testing device allowing the technique to work even in poorly resourced locations, the innovation will be ready to scale.

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Nurami Medical lands $6M making regenerative bandages for post-surgery recovery

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The Israeli MedTech company develops post-surgical application-tailored synthetic graft solutions to help protect the brain and accelerate patient recovery time…

Israeli MedTech startup Nurami Medical, which develops post-surgical soft-tissue healing solutions, announced a $6 million Series B funding round. The investment was led by Almeda Ventures, with participation from Leon Recanati’s private equity investment company, GlenRock.

Targeting FDA and CE approval

Nurami Medical‘s technology is based on biodegradable, synthetic nanofibers with sealing properties for improved soft tissue healing. The company has set out to revolutionize the regenerative medicine industry by providing both patients and physicians an effective application-tailored patch or surgical sealant solution. According to the company, in addition to its initial product offering – ArtiFascia – it is also lining up future projects for tissue regeneration solutions, which Nurami notes are part of a $20 billion market.

Regarding the ongoing clinical trials, co-founder Dr. Amir Bahar, a multidisciplinary entrepreneur and Nurami’s Clinical Director and Operations Manager said, “ArtiFascia’s clinical trial is being carried out at a number of European medical centers. This is a controlled, blind study, and as of yet, no adverse reactions have been documented.”

ArtiFascia is a patented, synthetic dural graft that protects the brain after neurosurgeries by boosting dura regeneration, while preventing cerebral-spinal fluid (CSF) leakage, to protect both the brain itself and central nervous system.

Nora Nseir Manassa, co-founder, co-CEO and CTO at Nurami adds, “Nurami is involved in ongoing efforts for the development of additional solutions for soft tissue repair and healing, for additional clinical indications, based on our technological platform which incorporates novel materials and unique manufacturing processes.”

Nurami Medical was founded in 2014 by uber-talented co-CEO and CTO Nora Nseir Manassa, COO Dr. Amir Bahar, and NGT3VC, a venture capital fund supporting early-stage life science startups. Previously, the company had raised $5 million from a number of Angel investors and the Israel Innovation Authority. The company relayed that the funding will be set towards completing clinical trials on ArtiFascia, and attaining both FDA and CE clearance. The clinical trial will test ArtiFascia in 90 patients, of which 13 have already been implanted with the ArtiFascia graft.

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