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Tech 2020: Non-Invasive Medical Nanotechnology

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Nanodiamonds: Non-Invasive, Slow-Release, Targeted Tumor Treatment

When many of us think of diamonds, our minds automatically turn to expensive jewelry. However, when broken down into the microparticulate level, diamonds can provide something far more valuable than ornamental art pieces you wear. At a size of four to five nanometers — roughly .00005 the width of a human hair—nanodiamonds are part of a cancer drug-delivery solution that researchers are exploring to create a non-invasive brain tumor treatment that overcomes issues in poor pharmacokinetics (i.e., the process by which treatments are absorbed, distributed, metabolized, and eliminated by the body) and chemoresistance (i.e., when cancers that previously responded to therapy begin to grow again).

Researchers at UCLA are using the unique properties of nanodiamonds to overcome the struggles in delivering chemotherapeutic treatment to brain tumors. One issue in brain tumor treatment at a pharmacokinetic level is that it is difficult for standalone chemotherapy drugs to penetrate the blood-brain-barrier (BBB)—a complex system of blood vessels whose purpose is to protect the brain from blood-borne infections and toxins. Treatment that does cross the BBB doesn’t stay concentrated long enough to be effective and is often met with chemo-resistence whereby the cells infected with cancer eject the cancer drug before it has time to work.

Nanodiamonds have unique characteristics that combat these two major issues in brain tumor treatment. While the BBB protects the brain from larger particles, the BBB fails to capture nanoparticles. With their incredibly tiny size, nanodiamonds can get past the BBB, close to cancerous masses, and overcome the pharmacokinetic hurdle standing in the way of effective brain tumor treatment.

Nanodiamonds also have a unique property whereby they are capable of binding to a wide array of bioactive molecules—including those used for cancer treatment. Researchers have been able to successfully bind slow-release chemotherapy agents to nanodiamonds, with promising results when injected into mice. When drug is delivered bound to nanodiamonds, the cancerous cells can’t eject them in the same way they can with standalone drug. Because the nanodiamonds work to keep treatment in place, the drug stayed in the tumor longer and in greater concentration. Less drug was also found in tissues outside the tumor, which reduces toxic side-effects.

If researchers can learn enough about the purity, surface chemistry, dispersion quality, temperature, ionic composition, and other environmental factors that mediate nanodiamond drug absorption and desorption, the implications for noninvasive ways to treat cancers—and a whole other host of infections and diseases—could be absolutely revolutionary.

Diabetes Patch: Non-Invasive Blood Glucose Monitoring

According to the International Diabetes Federation, nearly 425 million people in the world were living with diabetes in 2017. Ninety percent of diabetes cases worldwide are type 2—the type of diabetes where the body develops insulin resistance. In type 2 diabetes, insulin production drops as a result of an exhausted pancreas; cells in muscles, fat, and the liver become unable to absorb glucose; and blood sugars skyrocket. The short-term effects of high blood sugar can be mild, resulting in fatigue, nausea or dizziness, while the long-term effects of untreated diabetes include liver damage, heart attack, stroke, blindness, and gangrene, amongst others.

Ensuring that diabetes doesn’t lead to either short- or long-term consequences requires careful monitoring. At this point in time, monitoring requires diagnosed diabetes sufferers to prick their fingers once, and sometimes twice per day to monitor blood-glucose levels. The impact of daily finger-sticking can include scarring, callous formation, and loss of sensitivity in the fingertip. While needle technology has reduced the amount of pain experienced by diabetics who monitor blood glucose daily, pain hasn’t been fully eliminated from the process.

Freedom from the finger-stick may be on the horizon thanks to research being done on a wearable patch that extracts glucose in a completely novel way. Researchers from a multidisciplinary team at the University of Bath have developed a patch-based monitoring system that extracts glucose measurements from fluid in between hair follicles. The patch uses an array of mini sensors, and uses a small electric current to extract the fluid into reservoirs where the glucose levels are measured. The patches function autonomously; have flexibility to take measurements every few minutes to every few hours; and in the future may even be able to send real-time blood-glucose information to a wearer’s smartphone.

Patches were initially tested on pig skin and have been successfully tested on healthy human test subjects as well. Before the patch is released to market, the sensor arrays must be optimized, the patches must work for a full 24 hours, and the patches must pass through the customary clinical trial process.

So while those with diabetes must continue to use invasive forms of glucose measurement, freedom from the finger-stick may soon be a non-invasive reality.

Biodegradable Non-Invasive Nanoneedles: Better Transplantation Outcomes

For those experiencing end-stage disease conditions related to the liver, heart, kidneys, or lungs, transplantation from living or deceased donors may be the only treatment options available.

The absolute best-case scenario for transplantation is having a donor who is an identical twin, as the two bodies share a genotype, making the likelihood of rejection decrease. Because most people do not have an identical twin, the allograft (i.e., the tissues or organs being transplanted from another human with a different genotype) are subject to rejection both immediately and over time. One way scientists are looking to combat this rejection is by modifying cells to be more hospitable hosts to transplanted organs.

Injecting new nucleic acids (i.e., DNA, RNA, etc.) into a cell is one of the noninvasive avenues being explored to increase the acceptance rate of foreign organs into a host body. RNA treatments have the possibility to reduce the body’s immune response, reduce the production of the T-cells that would reject the foreign organ, and thereby increase the likelihood that the organ will have long term efficacy after transplantation. Effectively implementing nucleic acids into a cell, however, is tricky—and many methods result in cell death, instead of the hoped-for outcome of a cell that won’t attack the graft.

Researchers at the the Imperial College London (ICL) and Houston Methodist Research Institute (HMRI) have developed a nano-scale biodegradable solution that has potential to overcome this particular hurdle if the technology can be transitioned from mice to humans. Using a tunable array of nanoneedles (i.e., a collection of needles whose operation can be altered in a controlled manner), the scientists were able to deliver a combination of DNA and siRNA into the cell with reduced risk of cell death and cell damage, with an efficiency of 90 percent. The nanoneedles broke down after two days, leaving behind a non-toxic substance, and treatment resulted in a six-fold increase in blood being delivered to the tissues targeted, and the growth of blood vessels 14 days following its conclusion.

If this method can eventually be transitioned to human-scale use, the hope is that the bodies of those undergoing this form of cellular treatment will create the vasculature needed to support the new organ. In addition, the high level efficacy of nucleic acid transfer by the nanoneedles has potential to open up treatment avenues that eliminate or reduce the need for the use of immunosuppressive therapy, which can put patients at higher risk for infection following transplant.

Non-Invasive Prostate Cancer Detection: Reduce or Eliminate the Need for Biopsies

Each year, almost 175,000 men are diagnosed with prostate cancer in the United States. The road to determining whether or not a man has prostate cancer when asymptotic is through a prostate-specific-antigen (PSA) blood test. If, through the reading of this blood test, prostate cancer is suspected, the only way to diagnose prostate cancer is through a prostate biopsy, where a small sample of the prostate is removed with a needle for examination. If cancer is found, more biopsies are often required to track the progression of the cancer in the body. That’s two invasive procedures just for detection—and many more if cancer is found.

To eliminate the need for a blood test, Israeli Scientists at the Kaplan Medical Center in Rehovot have developed a urine-test that actually outperforms current PSA tests in providing accurate positive results. Using CellDetect technology by Micromedic, scientists use a proprietary plant extract and generic dyes on the urine sample which turns suspicious cells red-purple when examined under a microscope.

In addition, when the cancer is further along, the dye can help scientists to determine differences in cell morphology (shape) as well. With the ability to see suspicious cells and discern their shape, scientists can more accurately predict whether or not prostate cancer is present. While this method still requires biopsy for diagnosis, the number of unnecessary biopsies are reduced.

Scientists at Washington State University are working to eliminate the need for biopsy for prostate cancer (and potentially other forms of cancer as well) through a novel system geared to attract prostate cancer-specific exosomes (i.e., intercellular communicators that play a role in cancer progression) like a magnet.

Using a silicone nanostructure support armed with a ligand (i.e., a molecule that forms complex bonds with another molecule) that binds to prostate-cancer specific antigens, scientists are able to isolate the exosome for analysis. The benefit to this method is that you can use non-invasive samples like urine for the analysis. Without need for biopsy, scientists can analyze the exosomes to determine the cancer’s molecular composition and the cancer’s progress. Doctors can then use this information to predict the most effective course of treatment for a patient.

Although currently only in testing with prostate cancer, scientists are optimistic that by isolating exosomes for other types of cancers, this kind of non-invasive testing could have broader applications.

Non-Invasive Electrical Stimulation: Help Quadriplegics to Regain Motor Function

Quadriplegia is paralysis caused by injury or illness where all four limbs and the torso are impacted. In some cases, quadriplegics lose all use of these parts of the body, while others experience partial loss. In the United States alone, almost 5.4 million people live with paralysis, and 1.5 million are living with spinal cord injuries. While there is some research into implants that mediate the return of function, finding a non-invasive solution is a monumental task that researchers are UCLA are exploring.

Based on findings that applying non-invasive electrical stimulation at multiple sites on the spine induced involuntary stepping movements, researchers applied electrical stimulation to multiple sites on test subjects to try to improve functioning in the hands. Applying electrical stimulation using electrodes placed on the skin between vertebrae C3 and C4 (as well as C6 and C7), scientists applied 30hz of frequency in 1.0 millisecond phases. Following electrical stimulation, subjects underwent a one- to two-hour hand-grip training session. After eight treatment sessions, the average amount of improvement in grip strength was 325 percent and some patients experienced improvements in autonomic functioning as well.

Subjects in this study were all those experiencing paralysis for longer than a year and no patients reported pain as a result of the treatment. Of the two test subjects who returned for follow-up 60 days past treatment, their grip strength was maintained. Researchers report that this treatment yielded the largest reported recovery of use of hands than any reported in the past. Because of the inexpensive and non-invasive nature of the treatment, researchers are hopeful that the technique can be used broadly, in poor communities, and without advanced medical facilities.

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