Nanomedicines and their revolutionary mode of administration, falling under the infinitely small, are making much talk about them. It is no longer a question for the patient to receive the active principle by swallowing, for example, a tablet. This time, the healing molecule is encapsulated in a particle, the size of which is on the order of a billionth of a meter, then injected into the patient using an injection or an infusion.
Potentially, nanomedicine could involve many diseases. However, it is most advanced for cancer. In tumors, nine nanomedicines are already marketed around the world, according to the census published in November 2016 in the journal Nature. Clinical trials are currently being conducted for 15 other products, 5 of which have reached phase III - that is, they are close to the market.
This type of treatment offers two major advantages in the fight against cancer. More targeted, it damages healthy tissue less than chemotherapy and radiation and entering the center of tumor cells; the active ingredient is more effective. The problem that remains to be solved today is to get the maximum amount to cancer cells, which are to say to lose as little as possible en route.
In cancer, the development of new drugs faces several major challenges. Indeed, the chemotherapy and radiation currently used to prevent the proliferation of cancer cells but also induce toxicity towards healthy cells. For this reason, these treatments must be treated in a reasonable manner at the expense, sometimes, of their effectiveness. In addition, in the case of cancer with metastases, more than 90% of patients see their treatment fail because of the appearance of resistance. In other words, the genetic behavior of cancer cells changes, allowing them to oppose the action of anticancer drugs.
The nanomedicine must overcome many of these obstacles. It consists in transporting a molecule with pharmacological properties inside the body due to nanotechnology (or nanoparticle), that is to say, tiny particles serving as a means of transportation. They are made of materials that are inert towards the organism. These are generally biodegradable. In this case, the products of degradation are excreted by the human body - and must be devoid of toxicity.
These nanoparticles are injected into the patient's blood system via an infusion, for example. The nanoparticles transport this substance to cancer cells, which avoids most of the deleterious effects that the drug could have on healthy tissue. Furthermore, when an active substance is in the form of a nanomedicine, it is encapsulated and therefore protected against degradation throughout its journey through the body. These particles can, however, be recognized as external by the immune system, thus risking being destroyed in white blood cells called macrophages, especially in the liver.
To remedy this problem, the researchers carry out a simple modification of the surface of the nanoparticles, which makes them "stealthy" vis-à-vis our immune defenses. These are generally qualified as second-generation nanoparticles.
Passage through the wall of blood vessels facilitated by their small size
Once the nanoparticles have reached the vicinity of the tumor, they must still cross the wall of the blood vessels used to irrigate and supply it. These new vessels are fortunately more permeable than normal vessels. The tiny size of the particles allows them to pass easily, especially when they are circulating in the bloodstream for a long time - increasing their chances of encountering these porous vessels.
Thus, the longevity of these particles allows them to accumulate at the very center of the tumor. These nanoparticles penetrate into cancer cells and release their substance with pharmacological properties there.
Researchers have developed a nanomedicine against this pathology, called Livatag. It is currently in phase III clinical trial. This drug recently received from the FDA, the health authority of the United States, the statute “fast track,” an accelerated procedure of authorization reserved for the treatments concerning a severe pathology or putting in life-threatening of the patients.
Animal tests show that this specific model of drug delivery reduces toxicity and improves pharmacological efficacy. A survival rate of 88.9% was observed after 18 months of treatment with nanomedicine, against 54.5% with more conventional treatment, according to the results of the trial.
For researchers, however, the Grail consists in making the nanomedicine more selective vis-à-vis cancer cells to guide it towards its target, like a homing missile. For this, as the work of researchers have shown that we can add molecules to the surface of nanoparticles that recognize only cancer cells. Researchers are exploring this track of third-generation nanoparticles, with the aim of targeting cancer stem cells highly resistant to conventional chemotherapy.
An alternative approach, there also developed by medical researchers, is to recognize nano drugs by natural molecules in the body that will lead them to their target. Certain lipid nanoparticles allow this "carpooling." They will associate with lipids in the human body to be guided to tumor cells which have receptors for these molecules. Among the ways of progress, scientists are trying to combine nanomedicines with physical methods that make it possible to increase the speed and the quantity of drug released at the level of the tumor. Thus, the administration of the drug can be triggered remotely by the emission of ultrasound.
Nanomedicines are also used as a heat source to increase the effectiveness of conventional radiotherapy or chemotherapy treatments.
Based on this concept, the European company Nanobiotix has designed a nanoparticle called NanoXray, made of hafnium oxide. This compound is capable of emitting many electrons when it receives X-rays. This causes significant heating and thus significantly amplifies the effectiveness of radiotherapy on a tumor, reducing the necessary dose of radiation.
It is in this promising context that the NanoTheRad project is worth considering. It will mainly consist of combining radiotherapy with nanoparticles capable of making tumors more sensitive to radiation, and of evaluating this approach in small animals first. This program, bringing together many teams, including clinical doctors, should lead to applications in patients within a few years.