Precision magnetics could be game-changer for therapy-resistant brain cancers

Posted on April 11, 2023

Summary:

New mechanical nanosurgery approach developed by SickKids and U of T researchers uses nanotechnology and precision magnetics to destroy tumour cells.

Artistic rendering illustrating how the new approach target cancer cells from inside the tumour, sparing healthy tissue in the process.

What if you could fight cancer from inside the tumour?

SickKids researchers are pioneering a novel approach called mechanical nanosurgery to get at cancer cells from inside the tumour using precision magnetics.

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 tumour cells, called mechanical nanosurgery, even for aggressive, chemoresistant cancers.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite various treatment options that exist, including surgery, radiotherapy, and chemotherapy, the median survival time for patients is only around 15 months.

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

In a study published in Science Advances, Dr. Xi Huang, a Senior Scientist in the Developmental & Stem Cell Biology program at SickKids, and Dr. Yu Sun, Professor of Mechanical Engineering and Director of the Robotics Institute at U of T, present a new approach to treat chemoresistant GBM using precision magnetic control in a process they call mechanical nanosurgery.

“Through the use of nanotechnology deep inside cancer cells, mechanical nanosurgery is a ‘Trojan Horse’ approach that could allow us to destroy tumour cells from within,” says Huang, whose previous research demonstrating that brain tumour cells are mechanosensitive helped to inform the approach. “By combining our expertise in biochemistry at SickKids and engineering at U of T, we’ve 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 Centre, the mouse model used in the study showed that the mechanical nanosurgery process reduced GBM tumour size universally, including in TMZ-resistant GBM.

Mechanical nanosurgery explained

Magnetic carbon nanotubes (mCNTs) are a form of nanomaterial – microscopic cylindrically-shaped tubes made of carbon and, in this case, filled with iron that becomes magnetized when activated by an external magnetic field. In the study, the research team coated mCNTs with an antibody that recognizes a specific protein associated with GBM tumour cells. Once injected into the tumour, the antibodies on the mCNTs cause them to seek out tumour cells and are absorbed by them.

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

A diagram of a cylinder with a hexagon pattern appears on screen. There are small blue circles on the cylinder that are labelled “iron”.

Text on screen: Mechanical nanosurgery is a new technique that uses microscopic cylindrically-shaped tubes made of carbon and filled with iron, called magnetic carbon nanotubes (mCNTs).

Several Y-shaped figures attach to the cylinder. These figures are labelled “antibodies”.

Text on screen: These mCNTs are coated with antibodies and injected directly into the tumour site.

The cylinder and its antibodies fade away and the screen transitions to a closeup illustration of a brain from the side. In the brain, there is small round shape that is circled and labelled “tumour site”.

The screen zooms into the tumour site, briefly showing a collection of tumour cells (represented as round shapes, each with a small, dark circle inside). One of the tumour cells is isolated, while the rest fade out from the screen.

Cylinders coated with antibodies float toward the tumour cell and latch onto it. The cylinders move into the tumour cell.

Text on screen: The antibody-coated mCNTs specifically target tumour cells and are absorbed by the cells.

The tumour cell fades away and the screen transitions to the illustration of the brain with the tumour. To the left and right of the brain, two sets of rings radiate outward in waves.

Text on screen: When the mCNTs are in place, scientists activate a magnetic field from outside the brain.

The brain illustration fades away and a closeup of the tumour cell with the cylinders appears. As the rings continue to radiate outward in waves on both sides of the tumour cell, the cylinders inside the cell start spinning.

Text on screen: This magnetic field makes the mCNTs spin and destroy tumour cells from within, while sparing healthy brain tissues.

The spinning cylinders tear apart the tumour cell from the inside until the tumour cell fades away.

Text on screen: This destroys or reduces the size of the tumour, including chemoresistant tumours that do not respond to conventional therapy.

The closeup illustration of the brain with the tumour appears on screen. The round shape representing the tumour site decreases in size until it is no longer visible.

Text on screen: Visit sickkids.ca/mecnano to learn more.
Xian Wang et al. (2023) "Mechanical nanosurgery of chemoresistant glioblastoma using magnetically controlled carbon nanotubes." Science Advances.

Exploring applications beyond brain cancer

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

“Theoretically, by changing the antibody coating and redirecting nanotubes to the desired tumour site, we could potentially have a means to precisely destroy tumour cells in other cancers,” says Huang.

This research was funded by the Canadian Institutes of Health Research (CIHR), National Sciences and Engineering Research Council, Ontario Research Fund, Canadian Cancer Society, Concern Foundation, b.r.a.i.n.child, Sontag Foundation, Meagan’s HUG, Ontario Institute for Cancer Research, Brain Tumour Foundation of Canada, Hopper-Belmont Foundation, Arthur and Sonia Labatt Brain Tumour Research Centre, Garron Family Cancer Centre, and SickKids Foundation.