Nanotechnologies to simplify the lives of patients

Based on the use of nano-objects, that is to say a few billionths of a meter (100,000 times less than the thickness of a hair), this incredible revolution is not a utopia but indeed a reality for many patients today. And that's just the beginning. "The development of nanotechnology in health is starting to become significant," notes Patrick Boisseau, head of the nanomedicine program at CEA ¹ and president of the European nanomedicine technology platform. More than 165 new drugs and 65 medical devices have already emerged. And 122 others are in clinical trials, "a must before obtaining their marketing authorization. In fact, the fields of application of this medicine more preventive, more precise and more personalized are innumerable: cardiovascular disorders, renal or bone pathologies, sterility, dysfunction of the brain ... But, at the moment, the one of the main therapeutic areas remains oncology since conventional treatments do not always prove efficient and cause unwanted side effects that are often devastating.

THE LIFE OF SIMPLE DIABETICS

Controlling your blood sugar, by dosing the blood sugar level several times a day, is a terrible constraint, even though the self-monitoring devices have evolved considerably. This ordeal may soon be a bad memory thanks to the innovation of American engineers at Brown University (Rhode Island): a device packed with nanotechnology able to measure blood glucose in saliva. More sensitive than current glucometers, it detects the minute daily variations in the sugar content of saliva, which is the perfect reflection of blood glucose but at a concentration one hundred times lower. For diabetics, the gain in comfort of life will be invaluable: no need to prick oneself. It will be enough to soak the device's biochip with saliva, then replace it in the reader.

1. Commissariat for Atomic Energy and Alternative Energies.

The Trojan horse technique with nanotechnologies

Thus, some aggressive tumors, such as primary cancer of the liver, are resistant to chemotherapy because their malignant cells reject the active ingredient used against them. "That's why we've developed a lure system (the Livatag®) that allows it to move forward masked," says Judith Gréciet, general manager of the laboratory BioAlliance Pharma. These are biodegradable nanoparticles that carry the drug to the liver and bring it inside, like a Trojan horse, into diseased cells. There he is released near the nucleus and can easily destroy it. For the 400 patients with invasive liver carcinoma who have benefited from this protocol, the result is visibly positive: they show a survival rate more than doubled, of thirty-two months on average, compared to fifteen months of ordinary. Other tiny drug carriers are equipped with a GPS function.

This is the case of Lipidots® developed at CEA. Under this scholarly name lie emulsions of tiny droplets of lipids and wax capable of encapsulating active ingredients. Much smaller than red blood cells, "these nanospheres are ideal for delivering targeted insoluble drugs in injectable form," says Patrick Boisseau. They are so small that they circulate without damage in the blood vessels, even the finest, to reach the diseased tissues in which they cling, then release their charge.

The targets of these homing missiles can be varied, from lymphomas to tumor foci to inflammatory areas ... As for their advantages, they are really considerable: not only do these nano-vehicles protect the active principle external aggression, which increases its life, but they also reduce the doses administered (and therefore the adverse effects) since the drug is not diluted throughout the body but distributed exclusively where its intervention is necessary. As many pharmaceutical companies are on the spot, some patients should start benefiting within two to three years.

Nanotechnology X-ray lightning rods

Nanotechnology is also pushing the boundaries of radiation therapy, one of the cornerstones of cancer treatment. "60% of patients are treated with high-energy X-rays, but many people can not receive the doses required to destroy their entire tumor because the damage to surrounding tissues would be far too great", observes Laurent Levy, president of Nanobiotix, a French nanobiology and innovative SME company. Elected 2013 Entrepreneur of the Year by the American University of Buffalo, New York, this researcher found an absolute weapon to leverage the power of radiation without touching healthy cells. Called NanoXray, its invention is based on the use of lilliputian particles of hafnium, an ultra-reactive element to radiation. "Injected locally or by blood before the first session of radiotherapy, they are introduced into the cancer cells and concentrate the rays on them," says Laurent Levy. A bit like a lightning rod attracts the lightning to him, which amplifies significantly the effectiveness of the treatment. Thus, for irradiation of standard intensity, the dose received by the tumor is nine times greater than before!

What to overcome many recalcitrant cancers without changing the course of care practices. Several patients with soft tissue sarcoma (a rare cancer that develops in the muscles or fat) have already been treated (with success) at Gustave-Roussy Hospital in Villejuif. The technique is also being validated at the Institut Curie in Paris on advanced head and neck cancers. And it will soon start the onslaught of cancers of the colon, prostate, breast and lung.

Nanotechnologies help fragile hearts

This promising medical nanorevolution is also aimed at fragile hearts. Indeed, after having one or more infarcts, the damaged heart muscle sometimes struggles to contract properly. In this case, the graft remains the only solution, but the technique is expensive and relatively uncertain, especially because of the limited number of organ donations.

The use of autonomous artificial hearts, like that of the Carmat company implanted for the first time last December on a patient, is still in its infancy. And the injections of cardiac stem cells that have been under consideration for several years to restore vital beats are hovering over a major obstacle: few of the cells administered reach the damaged site. Most are dispersed throughout the body and eventually neutralized by the liver or captured by the lungs. This lock should be lifted soon thanks to the doctors at the Georges Pompidou Hospital in Paris.

Their strategy: to couple the healing cells to iron nanoparticles so that they can be directed to their target from the outside using a magnet. Clever!

Researchers at Inserm ^{2 are} tackling atherosclerosis, a widespread pathology characterized by the deposition of fat plaques on the inner lining of the arteries. By growing bigger, they end up impeding the blood circulation. Worse, some become detached and will obstruct vessels, which promotes the occurrence of myocardial infarction or stroke. Hence the idea of ​​using nanoscopic lookouts that can regularly inspect the arteries of people at risk to report the presence of any suspicious accumulation.

Developed in the framework of the European program NanoAthero, this traveling sentinel will be able to make a double blow: "To locate the plates of atheroma and to stabilize them immediately by pouring on them a treating agent", underlines Dr. Cédric Chauvierre, researcher in the hospital Bichat, in Paris. Blood clots in formation may likewise be detected and dissolved before they clog the arteries.

2. National Institute of Health and Medical Research

Gold vaccines, silver antibiotics and nano-sponges against venom

GOLD VACCINES AND ANTIBIOUS SILVER

As they raise more and more concern among the population, vaccines also have an interest in reforming in depth. The safety of their adjuvants, used to strengthen the immune response of the body, is particularly implicated in that many contain aluminum salts suspected of inducing chronic fatigue and trigger Alzheimer's disease . Nanotechnologies, whose potential seems unlimited, offer them a tremendous opportunity for change. At this infinitesimal scale, the properties of materials are often different from those we know.

This is the case of gold which, reduced to its proper portion, activates our natural defenses. Based on this discovery, US researchers at Vanderbilt University in Nashville, Tennessee are refining a new generation of gold nanotube vaccines. These small nano-straws are real little "jewelery" coated with specific viral proteins and whip up our immune system better than all the adjuvants currently used. According to a study published in June 2013 in the journal Nanotechnology , they are particularly effective against Respiratory Syncytial Virus (RSV), the microbe of the famous bronchiolitis that affects many children each winter and is responsible for several hundred thousand deaths every year in the world. At the University of Laval, Quebec, other nanotubes are being tested as alternatives to adjuvants for seasonal influenza and hepatitis B vaccines. Dr. Denis Leclerc, co-author of these works, their toxicity would be much less than that of aluminum used in traditional vaccines.

Not content with preventing infections, nano-drugs can also eradicate them. This is good news because our overconsumption of antibiotics has led to the appearance of a large number of resistant germs. More than 70% of nosocomial infections contracted in hospitals, for example, no longer respond to at least one class of antibiotics. Worse: some strains become totally indomitable ... unless exposed to nanoparticles of money!

Strangely, these have de facto amazing bactericidal properties: they weaken the outer membrane of microbes and empty part of their contents. A feat used by food production plants to sanitize all surfaces in contact with food: refrigerators, cutting boards, storage shelves ... Their medical use, orchestrated at Harvard University, could allow us to to muzzle the bacteria entered into resistance.

And to rehabilitate accordingly a panoply of antibiotics that are not sufficiently effective solo. Attached to nanoparticles of silver, they would be a hundred to a thousand times faster against the offensives of pathogenic germs. The results of the tests conducted on mice with fatal peritonitis prove it. Only 10% of rodents treated with antibiotics alone (vancomycin) survived, compared to 90% of those who received a cocktail of antibiotics and nanoparticles of silver.

NANO-SPONGES AGAINST THE VENINS

According to WHO, bites of poisonous snakes are responsible for 125,000 deaths a year worldwide. And the stings of wasps, bees and hornets of a thousand or so. If the toxins inoculated by these animals were neutralized before exerting their ill effects, we would not shake their approach any more. The nano-sponges developed at the University of California, San Diego, should make this dream possible. Enveloped with a fragment of red blood cell membrane, to pass unnoticed in the bloodstream, they are made of a biocompatible polymer that absorbs venoms and immediately reduces them to crumbs. Clever and terribly effective.

Diagnose the invisible with nanotechnologies

Another great field of choice for nanomedicine: ultra-early detection of diseases. It is indeed at the level of molecules that appear the first signals of organic dysfunctions likely to lead to the development of a pathology. Before the first-ever physical symptom occurs, poorly-developed cells emit SOS or produce aberrant proteins.

"The miniaturization offered by nanoparticles makes it possible to capture, isolate and measure these biological markers, witnesses of the very early stages of the disease," says Patrick Boisseau, head of the nanomedicine program at CEA. These analyzes can be done in a few hours in fully automated mini-laboratories from a sample of blood, saliva, urine or tear, or in vivo, that is to say directly in the body of the patient. For us, the advance is dizzying because the more an affection is detected upstream, the easier it is to heal quickly and the less it will leave behind. Biochips, biological analysis devices hardly bigger than a fingernail, are already able to detect almost instantly several tens of markers at the same time: inflammation, microbial infection ...

The genesis of certain cancers seems even detectable in our breath directly using electronic noses riddled with nanocomposants. Tumors emit specific volatile organic molecules that are found in our breath. It is therefore enough to exhale in a small box, in the manner of a breathalyzer, so that the verdict falls. Such devices already exist. One is being validated at the University of Bari, Italy, to reveal the presence of stammering colon cancers. Another is being refined at the University of Cleveland, USA, to detect early lung cancers. Bluffing!

Nanotechnology in our plates and for the health of the teeth

Nanos in our plates?

Hard to say considering the omerta of the industrialists. Fearing the boycott of consumers, they evade the issue, despite the obligation since 2013 to report to the authorities products containing it. According to the inventory drawn up by the Washington-based Woodrow Wilson International Center, there were already in 2011 more than 360 products incorporating nanos in Europe, including 10% in the food sector: nutritional supplements, slimming products, coating of bottles of Beer ... Not to mention the nanoparticulate additives, such as titanium dioxide (E171), a common dye of candies (chewing gum, sweets, ice cream), and silica oxide (E551) used as anti-caking agent in tomato sauces and vinaigrettes. Although nanos, they are not classified as such. However, a German study * showed in 2010 that they damaged the intestinal cells. For greater transparency, the presence of nanoparticles must imperatively be mentioned on the packaging of food products from December 2014.

* Institute for Umweltmedizinische Forschung, Düsseldorf.

REGENERATING LEAD

No more dental amalgams that just plug the holes? A team of researchers at the University of Maryland in Baltimore has been developing a revolutionary composite material based on calcium phosphate, ammonium and silver nanoparticles for a few months now. In addition to treating the spoiled tooth, it regenerates the missing tissues and remineralizes them to form a healthy quenotte. Better: it also controls the balance of bacteria populations living in the mouth to prevent the formation of new caries. Tests are planned on animals and human guinea pigs, in partnership with the Brazilian university Ceará.