Precision magnets could be a game changer for therapy-resistant brain cancer

April 11, 2023

(Nanowerk News) Scientists at The Hospital for Sick Children (SickKids) and the University of Toronto (U of T) have combined forces to develop a new approach to potentially treat tumor cells, called mechanical nanosurgery, even for aggressive, chemotherapy-resistant cancers.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite the various treatment options available, including surgery, radiotherapy, and chemotherapy, the average patient survival is only about 15 months.

The current global standard of care for GBM patients includes chemotherapy using a drug called temozolomide (TMZ), which extends a person’s life expectancy by about two months compared to patients receiving radiotherapy alone. However, GBM cells may develop resistance to TMZ over time, reducing its efficacy and increasing the likelihood of tumor recurrence.

In a study published in Science Advances (“Mechanical nanosurgery of chemoreresistant glioblastoma using magnetically controlled carbon nanotubes”), dr. Xi Huang, Senior Scientist in Stem Cell Development & Biology program at SickKids, and Dr. Yu Sun, Professor of Mechanical Engineering and Director of the Institute of Robotics at U of T, presented a new approach to treating chemo-resistant GBM using precision magnetic control in a process they call mechanical nanosurgery. Artistic rendering depicting how mechanical nanosurgery, a new approach developed by SickKids and University of Toronto researchers, targets cancer cells from within the tumor, sparing healthy tissue in the process. (Image: Created by The Hospital for Sick Children research team using Midjourney)

“Through using nanotechnology deep inside cancer cells, mechanical nanosurgery is a ‘Trojan Horse’ approach that allows us to destroy tumor cells from within,” said Huang, whose previous research showing that brain tumor cells are mechanosensitive helped inform the approach. (Neurons, “Mechanosensitive brain tumor cells construct a blood-tumor barrier to mask chemosensitivity”). “By combining our expertise in biochemistry at SickKids and engineering at U of T, we have developed a potential new way to treat aggressive brain cancer.”

Developed with first author Dr. Xian Wang, current Assistant Professor at Queen’s University, former post-doctoral fellow in the Huang Lab and winner of a Lap-Chee Tsui Fellowship through the SickKids Research Training Center, the mouse model used in this study demonstrated that a mechanical nanosurgery process significantly reduces the size of GBM tumors. universal, including TMZ-resistant GBM.

How mechanical nanosurgery works

Magnetic carbon nanotubes (mCNTs) are a form of nanomaterial – microscopic cylindrical tubes made of carbon and, in this case, filled with iron which become magnetized when activated by an external magnetic field. In the study, the research team coated mCNTs with antibodies that recognize specific proteins associated with GBM tumor cells. Once injected into a tumor, antibodies in the mCNTs cause them to seek out tumor cells and be absorbed by them.

“Once the nanotubes are inside the tumor cells, we use a rotating magnetic field to mechanically mobilize the nanotubes to provide mechanical stimulation,” said Sun. “The force exerted by the nanotubes damages cellular structures and causes tumor cell death.”

Exploring applications beyond brain cancer

Huang’s partnership with Sun in the U of T Department of Mechanical Engineering continues to build on the study’s findings. As their research continues, they note that mechanical nanosurgery may have further applications in other types of cancer.

“Theoretically, by altering the antibody coating and directing the nanotubes to the desired tumor site, we could potentially have the means to precisely destroy tumor cells in other cancers,” said Huang.

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