Plus sur les nanotubes.

(Jan. 29, 2008) — Carbon nanotubes-cylinders so tiny that it takes 50,000 lying side by side to equal the width of a human hair-are packed with the potential to be highly accurate vehicles for administering medicines and other therapeutic agents to patients. But a dearth of data about what happens to the tubes after they discharge their medical payloads has been a major stumbling block to progress.

Des nanotubes de carbones si petits que cela en prends 50,000 cote-à-cote pour équivaloir à l'épaisseur d'un cheveu sont des véhicules potentiels pour administrer des médicaments.

Now, Stanford researchers, who spent months tracking the tiny tubes inside mice, have found some answers.

Studies in mice already had shown that most nanomaterials tend to accumulate in organs such as the liver and spleen, which was a concern because no one knew how long they could linger. But fears that the tiny tubes might be piling up in vital organs, like discarded refrigerators at the bottom of a rural ravine, can now be put to rest, said Hongjie Dai, the J. G. Jackson and C. J. Wood Professor of Chemistry at Stanford, whose research team has demonstrated that the nanotubes exit the organs.

Les études déja faites ont montré que la plupart du nanomatériel tend à s'accumuler dans les organes tels que le foie et les poumons ce qui pose un problème car personne ne sait combien de temps il peut résider là. Mais les peurs que le nanomatériel puisse s'Accumuler dans les organes vitaux sont dépassées d'après le docteur Hongjie Dai et d'autres qui ont démontré que le nanomatériel sort des organes.

Dai and his group found that the carbon nanotubes leave the body primarily through the feces, with some by way of the urine. ''That's nice to know,'' Dai said. ''This now proves that they do get out of the system.''
The full extent of the news, which is scheduled to be published the week of Jan. 28 in Proceedings of the National Academy of Sciences Online Early Edition (PNAS), is even better than that: The three-month-long study also allays worries that the nanotubes, by simply remaining in the organs for a long time, would prove toxic to the mouse.

''None of the mice died or showed any anomaly in the blood chemistry or in the main organs,'' said Dai, senior author on the PNAS paper. ''They appear very healthy, and they are gaining weight, just like normal mice. There's no obvious toxicity observed.'' The lack of toxicity of nanotubes in mice is consistent with a previous pilot study done by Sanjiv Gambhir, a professor of radiology at Stanford, and his research group in collaboration with Dai's group.

"Aucune des souris n'est morte ou n'a montré d'anormalité dans le sang ou dans les organes principaux."

''This is the first time anyone has done a systematic circulation and excretion study like this for nanotubes, and data on other nano particles is also scarce,'' Dai said. ''The excretion pathway may apply to other nano materials and may need to be looked at closely like this also.''
Previous research published by Dai's group has demonstrated the potential for using nanotubes in treating cancerous cells and targeting tumors in mice.

His group used Raman spectroscopy, a method of applying light from a laser beam that effectively ''illuminates'' the presence of the target molecules in the organs of the mice.

Being hit with light from the beam causes a detectable change in the state of a molecule's energy. Carbon nanotubes, composed entirely of carbon atoms that are mostly arranged in linked hexagonal rings, give off a strong signal in response to the beam. This allowed the researchers to pinpoint the position of the chosen molecules, as well as ascertain their abundance in the blood or organs.

Previous detection methods that relied on attaching fluorescent labels or spectroscopic tags to the nanotubes had yielded unreliable results. The attachments tended to either come loose from the tubes or decay over time spans ranging from a few days to only a few hours-far too short to reveal the ultimate fate of the nanotubes.

While knowing the carbon nanotubes will move through the digestive system at a healthy pace is critical to future practical applications, it is also crucial that the nanotubes not enter the digestive system too soon after being injected; they need to spend enough time in the circulatory system to find their way to their target location.

The key to fine-tuning the carbon nanotubes' speed of circulation turns on how the basic, bare-bones floor model is chemically accessorized.
''You can make the nanotubes circulate a very long time in the blood, if the chemistry is done right,'' Dai said. The researchers found that coating their carbon nanotubes with polyethylene glycol (PEG), a common ingredient in cosmetics, worked best.

They used a form of PEG with three little limbs sprouting off a central trunk. ''Those provide better shielding to the nanotube than just a single branch. Therefore, they interact less with the biological molecules around them,'' Dai said.

The team stuffed the PEG liberally into the linked hexagonal rings that compose the nanotubes, prompting Dai to describe the end result as resembling rolled-up chicken wire with feathers sticking out all over.
Though they may sound less than gorgeous visually, the feathery nanotubes turned in a beautiful performance in practical terms, Dai said. The coating of PEG made the nanotubes highly water soluble, which helped them to stay in the blood instead of being absorbed.

''They circulate in the blood for about 10 hours or so in mice, which seems to be a good length of time,'' Dai said.

The right chemical coating on nanotubes also can help ease them out of the mouse in a timely fashion, and the three-branched PEG was effective there, too.

Dai's earlier research demonstrated that nanotubes have promise for treating cancer with two different approaches. Once they have zeroed in on the target cells, shining light on the nanotubes causes them to generate heat, which can kill cancer cells. The other method is to rig the nanotubes to accumulate at targeted sites, where they can deliver medication from within the tubes.

Les recherches ont montré que les nanotubes promettent de traiter le cancer avec 2 différentes approches. Une fois qu'elles ont ciblé les celllules, une lumière réfléchissant sur le tube génère de la chaleur ce qui peut tuer les cellules cancéreuses. l'autre méthode est de diriger les nanotubes pour qu'ils s'accumulent sur un site ciblé ou ils peuvent liver la médication de l'intérieur du tube.
''[Carbon nanotubes] seem to be promising for biomedical applications and for potentially treating cancer, either using drugs or using the physical properties,'' Dai said. ''This is the reason we carried out the study of the fate of nanotubes in mice. I think this is really a very fundamental issue.''

(Jun. 16, 2008) — Researchers are testing a new way to kill cancer cells selectively by attaching cancer-seeking antibodies to tiny carbon tubes that heat up when exposed to near-infrared light.

Les chercheurs sont en train de tester un nouveau moyen de tuer les cellules cancéreuses en attachant des anticorps chercheurs à des microscopiques tubes de carbones qui ont la capacité de produire de la chaleur lorsqu'exposés à une source de rayonnement infra-rouge.

Biomedical scientists at UT Southwestern Medical Center and nanotechnology experts from UT Dallas describe their experiments in a study available online and in an upcoming print issue of Proceedings of the National Academy of Sciences.

Scientists are able to use biological molecules called monoclonal antibodies that bind to cancer cells. Monoclonal antibodies can work alone or can be attached to powerful anti-cancer drugs, radionuclides or toxins to deliver a deadly payload to cancer cells.

In this study, the researchers used monoclonal antibodies that targeted specific sites on lymphoma cells to coat tiny structures called carbon nanotubes. Carbon nanotubes are very small cylinders of graphite carbon that heat up when exposed to near-infrared light. This type of light, invisible to the human eye, is used in TV remote controls to switch channels and is detected by night-vision goggles. Near-infrared light can penetrate human tissue up to about 1½ inches.

Ce type de lumière invisible à l'oeil nu est utilisé par exemple dans les contrôles à distances pour les télés. La lumière peut pénétrer jusqu'à 1 pouce et demi dans le corps.

In cultures of cancerous lymphoma cells, the antibody-coated nanotubes attached to the cells' surfaces. When the targeted cells were then exposed to near-infrared light, the nanotubes heated up, generating enough heat to essentially "cook" the cells and kill them. Nanotubes coated with an unrelated antibody neither bound to nor killed the tumor cells.

Dans une culture de cellules lymphomatiques, les naotubes enduit d'anticorps se sont attachés à la surface des cellules. quand les mini-tubes furent exposées à la lumière, ils ont produit de la chaleur assez pour cuire les cellules cancéreuses et les tuer. Les cellules qui ne sont pas cancéreuses n'ont pas été affectées.

"Using near-infrared light for the induction of hyperthermia is particularly attractive because living tissues do not strongly absorb radiation in this range," said Dr. Ellen Vitetta, director of the Cancer Immunobiology Center at UT Southwestern and senior author of the study. "Once the carbon nanotubes have bound to the tumor cells, an external source of near-infrared light can be used to safely penetrate normal tissues and kill the tumor cells.

"Demonstrating this specific killing was the objective of this study. We have worked with targeted therapies for many years, and even when this degree of specificity can be demonstrated in a laboratory dish, there are many hurdles to translating these new therapies into clinical studies. We're just beginning to test this in mice, and although there is no guarantee it will work, we are optimistic."

Il y a encore beaucoup d'obstacles avant d'utiliser cette technologie sur des humains mais les chercheurs sont optimistes.

The use of carbon nanotubes to destroy cancer cells with heat is being explored by several research groups, but the new study is the first to show that both the antibody and the carbon nanotubes retained their physical properties and their functional abilities -- binding to and killing only the targeted cells. This was true even when the antibody-nanotube complex was placed in a setting designed to mimic conditions inside the human body.

Biomedical applications of nanoparticles are increasingly attracting the attention of basic and clinical scientists. There are, however, challenges to successfully developing nanomedical reagents. One is the potential that a new nanomaterial may damage healthy cells and organisms. This requires that the effects of nanomedical reagents on cells and organisms be thoroughly studied to determine whether the reagents are inherently toxic.

"There are rational approaches to detecting and minimizing the potential for nonspecific toxicity of the nanoparticles developed in our studies," said Dr. Rockford Draper, leader of the team from UT Dallas and a professor of molecular and cell biology.

Other researchers from UT Southwestern involved in the research were lead authors Pavitra Chakravarty, a graduate student in biomedical engineering, and Dr. Radu Marches, assistant professor in the Cancer Immunobiology Center. Authors from UT Dallas' Alan G. MacDiarmid NanoTech Institute were Dr. Inga Musselman, Dr. Paul Pantano and graduate student Pooja Bajaj. Two undergraduate students in UT Southwestern's Summer Undergraduate Research Fellowship program -- Austin Swafford from UT Dallas and Neil Zimmerman from the Massachusetts Institute of Technology -- also participated.

The research was supported by the Cancer Immunobiology Center at UT Southwestern, the Robert A. Welch Foundation, the Department of Defense and the Center for Applied Biology at UT Dallas.

Dr. Vitetta is a co-inventor on a patent describing the techniques outlined in the study.

voir aussi l'histoire d'un homme atteint du cancer à l'origine de cette thérapie