Harvard beauty scientist invents the magical "cancer"

Release date: 2016-07-29

Yunnan Baiyao Band-Aid, medicine is better and faster.

This slogan links the band-aid and the medicine, and the idea of ​​successfully creating a drug-enabled drug is deeply rooted in the heart. So this band-aid quickly succeeded in the small trauma market, and the streets and lanes were everywhere.

Recently, Dr. Natalie Artzi of Harvard Medical School led her research team to extend this concept to the field of cancer treatment. They invented a cancer-adhesive that contained three high-tech drugs that were successful in mouse models. On July 25th, their important research results were published in the top journal of materials science, Natural Materials (1).

Dr. Natalie Artzi

Dr. Artzi is not only an assistant professor at Harvard Medical School, she is also a researcher at the Massachusetts Institute of Technology (MIT). I have been working in the field of materials science for many years. About this cancer can be posted, it has to start from 2009.

Artzi, who was also a postdoctoral research assistant at the MIT Elazer R. Edelman lab, found that many patients had difficulty in healing or tissue adhesion due to adhesive problems after surgery, causing considerable pain to the patient. She believes that different organizations have different requirements for adhesives, so it is not appropriate for a kind of adhesive to be used in the world. So she tried to lead the team to solve this problem.

After a period of hard work, they invented a glue that can be adjusted according to the organization, so that the glue can adapt to the tissue in the best state. Currently, the glue can be used from the small intestine to the lungs. Stitching of the tissue. It is reported that the glue they invented is the first adhesive that can be adjusted according to the organization's attributes. Their research results are published in Advanced Materials (2), one of the top journals in materials science.

Although the glue they invented was already very good, they unexpectedly found that the glue had different effects on different diseases on the same tissue. For example, this glue has a better effect on intestinal cancer tissue than healthy intestinal tissue, but it has a better adhesion to inflammatory intestinal tissue than healthy intestinal tissue.

Artzi was surprised to find that this different manifestation is related to the content of collagen in the intestinal tissue under different conditions. Due to the particularity of the glue material, its adhesion is better in the tissue of high collagen. If the collagen of healthy tissue is used as the reference, the collagen content of intestinal tissue suffering from enteritis is low, and the collagen content of cancer tissue is very high. This explains the difference in the performance of glue on different diseases. Their important discovery was published in Science Translational Medicine in January 2015.

I never imagined that Artzi originally wanted to solve the problem of tissue adhesion after surgery, but in the end it was mistakenly linked to cancer. This is tantamount to scrambling to dig a gold mine. The magic of scientific research is nothing more than this. Since this glue has a strong adhesion to tumor tissue, can it be used to do something about the tumor? At this time, Artzi had the idea of ​​cancer sticking in his mind.

I don't know if Artzi is inspired by Yunnan Baiyao Band-Aid. She intends to make this hydrogel into a carrier, apply a layer of medicine on the surface of the carrier, and then firmly attach the hydrogel to the surface of the tumor. To allow the drug to penetrate into the tumor tissue accurately to achieve the purpose of treating cancer.

At the beginning, Artzi chose to challenge the most refractory triple-negative breast cancer. This kind of breast cancer has left almost no handle on scientists, and it has strong resistance and the patient's prognosis is very poor. Artzi chose to use multidrug resistant protein 1, MRP1 as a breakthrough point. She plans to use RNA silencing to get rid of genes that make breast cancer cells resistant. She first attached the RNA used to kill MRP1 to the gold nanoparticles, then implanted the nanoparticles into the hydrogel, and finally applied the hydrogel to the site where the tumor grew.

Subsequently, Artzi injected the mice with the chemotherapy drug 5-fluorouracil (5-FU), and they found that the tumor was reduced by 90% within two weeks. Just two months later, in March 2015, the Journal of the American Academy of Sciences published their important research results. This means that Artzi's idea of ​​using hydrogels as a tablet for the treatment of cancer drugs is feasible.

The picture hanging on the official website of MIT is attached with gold nanorods on cancer cells. The blue color above is Avastin antibody.

This first step is obviously not to make Artzi satisfied, and the cancer at this time can be far from the real therapeutic patch. Because its role now is to relieve the drug resistance of cancer cells, and there is no direct therapeutic effect. To make it work like a band-aid, Artzi must have a cancer-adhesive treatment. For this Artzi no less effort.

This time, in order to improve the efficiency of administration of RNA drugs, Artzi has developed an RNA delivery platform. They smashed the easily degradable RNA strand into a 3 helix, and in this state, the easily degradable RNA is surprisingly stable. With this technology, Artzi hangs two RNAs that inhibit the growth of cancer cells on gold nanoparticles and implants them into a hydrogel to make a treatable cancer patch.

This time, they still studied refractory triple-negative breast cancer. After the second-generation cancer patch was attached to the mouse, the tumor of the mouse was reduced by 90% in one week and the survival time was extended by 75 days. This treatment effect was far better than the traditional chemotherapy. Even compared with the first generation of "cancer paste", the effect is significantly improved, and the time to reduce tumors by 90% has been shortened by half. The results of this research were published in the top journal of materials science, Natural Materials, and only 9 months after the publication of the first-generation cancer-adhesive results.

Artzi's research is not smooth, and her dream has been realized. If you change to me, I should focus on finding a company or building a company to apply for clinical research. But Artzi still focused on finding new ways to further improve the treatment. Finally, I finally made the research results introduced in this article – the third generation of cancer stickers. (finally around the text)

This generation of "cancer stickers" reflects Artzi's ambitions, and she has taken this therapy to the extreme. Light therapy, gene therapy and immunotherapy, three high-tech together in this generation of cancer stickers.

A schematic diagram of the "cancer paste" inside the article, as well as various drugs hanging on the nanoparticles (Qianqian)

First, Artzi used two kinds of gold nanoparticles, one is gold nanorods and the other is gold nanospheres, both of which act as carriers of drugs, and have specific polypeptides that are pulled onto colorectal cancer cells. -1, this will avoid damage to healthy cells. Among them, gold nanorods are not only the carrier of drugs, but also a therapeutic method. It will heat under the illumination of near-infrared light and directly destroy cancer cells.

Secondly, Artzi hangs RNA that inhibits the expression of oncogene KRAS on gold nanospheres, which inhibits the growth of cancer cells.

Once again, Artzi hangs bevacizumab Avastin on gold nanorods, a drug that blocks angiogenesis and blocks the blood supply to the tumor by inhibiting the action of vascular endothelial growth factor to suppress tumor growth and metastasis. Currently, the FDA has approved Avastin for the treatment of lung, colon and rectal cancer, and the European Union has also approved it for the treatment of breast cancer.

What is the performance of such a three-pronged cancer label?

Artzi first applied the third-generation cancer to the recovery of cancer after surgery. Colorectal cancer, a cancer that poses a great threat to humans, is currently undergoing surgical resection. However, years of data have found that after surgical resection, the recurrence rate is 30%-50%.

In the mouse model of colorectal cancer, Artzi found that the cancer was not used after surgery, and the recurrence rate was about 40%. After the operation, the cancer was posted and there was no recurrence. This shows that cancer can completely destroy cancer cells that have not been removed.

Three PhDs (left to right) participating in the study, Joao Conde, Nuria Oliva, and Yi Zhang (Zhang graduated from Fudan University in 2007)

Cancer can be used not only for postoperative recovery, but also for direct treatment. When directly using "cancer paste", it can reduce the tumor volume by more than 90%, and the mouse can survive for more than 150 days. This is far superior to all other therapies, and is superior to "cancer paste" containing only one or two drugs. After these methods, the tumor volume is only 40%-60%, and the survival time is less than 45 days. The third-generation "cancer paste" with three drugs is obvious.

In fact, efficacy is only one aspect of the third-generation cancer that can be better than other therapies. In other respects, compared with traditional chemotherapy, cancer can only work on the tumor tissue it covers, and will not harm other tissues and organs. This was also verified in mice. Compared with surgical treatment, "cancer paste" is a non-invasive treatment. Moreover, Artzi's previous basic research shows that this therapy can be extended to other tumors located on the surface of the skin and under the shallow skin (such as bowel cancer, esophageal cancer, skin cancer and breast cancer).

After the hydrogel patch is attached to the lump on the mouse, it is illuminated with near-infrared light.

Artzi's vision is that cancer patches can be used in the treatment of some early cancers. In the case of colorectal cancer, when a doctor discovers an early tumor through colonoscopy, it is usually a minimally invasive resection. Artzi hopes that the way to treat this early tumor is not to remove it, but to attach a cancerous sticker to the tumor through a colonoscopy. Of course, for Artzi's new technology, the more demanding should be the postoperative suture, because if you use this patch to suture the wound after the removal of cancer tissue, it can effectively reduce the recurrence and metastasis rate of cancer.

It is reported that the Artzi team has formed a company last year, but it has not yet been made public. It is not difficult to imagine that the company that Artzi formed should be in the form of technical output. The fastest way to get into clinical use is to work with pharmaceutical companies to put drugs that have been approved by the FDA (such as Avastin, which is Roche's anticancer drug) on ​​this cancer.

Source: Singularity Network

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