Nanoparticles filled with drugs used to attack endometrial cancer in a laboratory study



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Nanoparticles targeting tumors filled with a drug that makes cancer cells more defenseless to the toxicity of chemotherapy could be used to treat a form destructive and frequently fatal endometrial cancer. according to a new study conducted by the University of Iowa College of Pharmacy.

Aliasger K. Salem, professor of pharmaceutical sciences at the UI, and Kareem Ebeid, graduate student in pharmaceutical sciences at the UI, work in the Salem laboratory. For the first time, the researchers combined traditional chemotherapy with a relatively new anti-cancer drug that attacks tumor cells resistant to chemotherapy, is loaded into small nanoparticles and creates an extremely selective and lethal treatment for cancer. The results of the three-year laboratory study were published in the journal Nature Nanotechnology. Photo by Tim Schoon.

For the first time, researchers integrated traditional chemotherapy with a comparatively new anti-cancer drug that targets tumor cells resistant to chemotherapy, both loaded into tiny nanoparticles, and created a highly selective and lethal cancer treatment. The results of the three-year laboratory research were published in the journal Nature Nanotechnology.

The new treatment could mean better survival rates for the approximately 6,000 American women diagnosed with type II endometrial cancer annually and it also means a vital step in the creation of targeted therapies against cancer. Contrary to chemotherapy, the existing standard in the treatment of cancer that exposes the whole body to anti-cancer drugs, targeted treatments deliver the drugs directly to the tumor site, protecting healthy tissues and organs and improving the efficacy of the drug.

In this particular study, we badume one of the greatest challenges in cancer research, which is the identification of tumors. And, for the first time, we were able to combine two different tumor selection strategies and use them to overcome the deadly type II endometrial cancer. We believe that this treatment could also be used to fight other cancers.

Kareem Ebeid, graduate student in pharmaceutical sciences, UI and principal investigator of the study

In his effort to develop an extremely selective treatment for cancer, Ebeid and his team started with tiny nanoparticles. In recent years, there has been increasing interest in the use of nanoparticles to treat cancer, mainly because of its small size. The tumors grow rapidly and the blood vessels they produce to fuel their growth are defective and full of holes. The nanoparticles are small enough to slide through the holes, allowing them to accurately target tumors.

The team then fed the nanoparticles with two anti-cancer drugs: paclitaxel, a type of chemotherapy that is used to treat endometrial cancer, and nintedanib, BIBF 1120, a comparatively new drug used to limit the growth of blood vessels of the tumor. However, in the UI study, the medication was used for a different purpose. In addition to limiting the growth of blood vessels, nintedanib also targets tumor cells with a particular mutation. The mutation, called loss of p53 function, alters the regular life cycle of tumor cells and makes them more resistant to the toxic effects of chemotherapy.

Chemotherapy destroys cells when they are in the process of mitosis or cell division. and tumor cells with the p53 loss of function mutation are often trapped in a state of limbo that slows down this process. Cancers that are resistant to chemotherapy are much harder to treat and have less encouraging results.

Nintedanib targets tumor cells with the p53 mutation of loss of function and forces them to enter mitosis and divide, at which point they die without chemotherapy effort. Ebeid says this is the first time that researchers use nintedanib to force tumor cells to mitosis and destroy them, a phenomenon researchers call "synthetic lethality."

Basically, we're taking advantage of the Achilles heel of the tumor cells: the loss of the functional mutation, and then sweeping and killing them with chemotherapy. We call this a synthetically lethal situation because we are creating the right conditions for mbadive cell death.

Kareem Ebeid

The treatment and cell death it stimulates can be applied to treat other cancers as well, including lung and ovarian cancers that also carry the mutation of p53 loss of function .

We believe that our research could have a positive impact beyond the treatment of endometrial cancer. We hope that since the medications used in our study have already been approved for clinical use, we can begin working with patients soon.

Aliasger K. Salem, Professor of Pharmaceutical Sciences, IU and corresponding author in the study

In the United States, incidence rates and mortality from endometrial cancer have increased in recent years, especially in the state of Iowa. Type I endometrial cancer, which feeds on the hormone estrogen, accounts for about 80% of new cases a year. Type II endometrial cancer is less common, accounting for approximately 10% to 20% of cases, but it is much more aggressive and accounts for 39% of annual deaths from endometrial cancer.

"For two decades, the standard therapy for endometrial cancer type II has been chemotherapy and radiation", says Kimberly K. Leslie, professor and president of the Department of Obstetrics and Gynecology UI Roy J. and Lucille A. Carver College of Medicine. " The possibility of a new treatment that is highly selective and highly effective is incredibly exciting."

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