Testing nanoparticles containing nucleic acid to treat brain cancer

Scientists at Northwestern University (USA) have researched and developed a new drug using organic nucleic acid attached to gold nanomaterials. This has important implications for cancer treatment and brain diseases.

The results of this study were approved by the FDA (US Food and Drug Administration) as a new drug for clinical trials to treat human brain tumors in January 2017.

This new drug can cross the blood brain barrier to reach tumors and will turn off the cancer-causing gene. This is a difficult challenge in treating brain diseases. In early 2017, the first phase of the project was conducted by scientists to test the accessibility of drugs to human tumors.

Glioblastoma represents a revolutionary new drug. The drug model made from organic nucleic acid chains clinging to gold nanoparticles can be applied to other neurological diseases such as Alzheimer's and Parkinson's, by neutralizing genes that lead to these diseases.

Glioblastoma represents a revolutionary new drug.

This is a rare drug that has been researched by a university, does not receive funding from any pharmaceutical company but is approved by the FDA for clinical trials.

"We want to bring drugs to patients as soon as possible. There are many patients with this disease but there is no cure," said Jay Walsh, vice president of research at Northwestern University .

"We know that this drug works in mice. We need to know whether it can cross the human blood-brain barrier and accumulate in human tumors ," Alexander Stegh, assistant teacher. Professor of neurology at Feinberg Medical School, Northwestern University said.

Stegh developed this drug with Chad A. Mirkin, a professor at the Weinberg College of Arts and Sciences and director of the Northwestern International Institute of Nano Technology (IIN). He also holds the Biotechnology Heritage Award of American biochemist George B. Rathmann.

"If the gold nanoparticles containing nucleic acid cross the blood-brain barrier and locate in the brain, its meaning goes beyond glioblastoma, the most common form of brain cancer , " Mirkin said. "This will complement the ability to treat brain diseases, including Huntington, Parkinson and Alzheimer's."

The new drug includes short segments of RNA specially arranged on the surface of spherical gold nanoparticles. It alters the genetic structure of tumor cells and reduces their ability to divide. The drug targets the effects of BCL2L12 gene , which is related to apoptosis, the mechanism that causes cell death according to the program.

Patients with goiter are treated with chemotherapy, radiotherapy and surgery. Even so, this disease has no definitive treatment. With 30,000 Americans, after being diagnosed with brain cancer, their remaining lifespan was only 14 to 16 months.

The new drug includes short segments of RNA specially arranged on the surface of spherical gold nanoparticles.

According to Dr. Priya Kumthekar, assistant professor of neurology and oncology at Feinberg School of Medicine: "We need an effective treatment to cure this deadly disease." Kumthekar is a researcher. The main study of the trial at Northwestern University, she will conduct a trial of 6-8 people with glioblastoma , the most common brain tumor.

The study will be tested on people who have relapsed after surgery to remove the tumor. They will receive an intravenous dose before surgery. After removal of the tumor, Kumthekar and her team will study the tumor to determine the strength of the drug needed to cross the blood-brain barrier.

"Animal studies show that this drug penetrates deep into tumors , " Kumthekar said. "We predict that case will also happen on the patient's tumor."

According to Dr. Frank Giles, former Northwestern University donor representative, "Northwestern focuses on providing better therapies to treat patients." 'Applying scientific knowledge is the way. best to develop new therapies, " Frank Giles said. Both Kumthekar, Stegh, Mirkin and Giles are members of Lurie Cancer Center.

'This is a complex, elaborate process that requires close coordination between research groups at Northwestern University and Northwestern Medicine Institute', said Ann Adams, vice president of research at Northwestern University. .

According to Dr. Leon Platanias, director of the Lurie Cancer Center: "This technology is amazing, we can take new, more effective approaches to treating brain tumors and other tumors in the future."

The birth of new drugs

Stegh and Mirkin have been collaborating since 2009 to solve the difficult problem of developing treatments for glioblastoma cysts. They first joined together through Northwestern University Cancer Center.

Mirkin's mission is to research and manufacture nucleic acids attached to gold nanomaterials, a new spherical form of DNA and RNA and non-human. In it, the nucleic acid cycle is designed to match the target gene.

For Stegh, his task is to study genes. In 2007, he and his colleagues identified the gene BCL2L12 that excelled in glioblastoma tumors. This is related to glioblastoma resistance.

Once inside the cancer cells, this drug neutralizes the pathogenic genes.

Operation mechanism

With the special properties of gold nanoparticles, the drug easily crosses the blood-brain barrier, approaching the brain tumor. Once inside the cancer cells, this drug neutralizes the pathogenic genes. The programmed cycle of RNA acts as a switch, which prevents cells from producing certain specific proteins involved in the disease. As a result, they will selectively destroy cancer cells and impair cell growth.

The key to the success of the new drug is the 3-D spherical structure of gold nanomaterials and the concentration of nucleic acids. Normal nucleic acids cannot penetrate cells or cross the blood-brain barrier, but nucleic acids attached to gold nanoparticles are possible.

Research results on animals

In 2013, Mirkin and Stegh were senior co-authors of an animal study published in Science Translational Medicine. Their team is the first to demonstrate the provision of an intravenous drug capable of disabling an important cancer-causing gene. It reduces the progression of tumors and increases the survival rate of mice with glioblastoma.

In mice with glioblastoma, about 1% of the injection dose was accumulated in brain tumor tissue. The great thing is that once in the brain, these spherical gold nucleic acids automatically focus on accumulating in tumor tissue. This is due to the ability of gold nanoparticles to accumulate in tumor tissue according to the pathways of blood vessels. Thus, the survival rate of these mice increased by nearly 20%, tumor size also decreased by 3 to 4 times compared to the control group.

The nanostructured platform in this study was developed by Mirkin at Northwestern University since 1996. This is the first time it has been realized that nanostructures are injected into an animal body that automatically finds targets. in the brain. This is highly effective for therapies. Northwestern University and a number of related researchers will benefit financially from the results of this study.