Mechanical Nanosurgery: Precise Magnetics Treats Aggressive Brain Tumors 2023

Even for aggressive, chemoresistant malignancies, scientists from The Hospital for Sick Children (SickKids) and the University of Toronto (U of T) have collaborated to develop mechanical nanosurgery as a potential treatment for tumor cells.

Glioblastoma is the most prevalent and aggressive form of primary brain cancer. Despite the availability of numerous treatment options, including surgery, radiotherapy, and chemotherapy, the median survival time for patients is approximately 15 months.

Average amount of time a patient lives is about 15 months.

The current global standard of care for GBM patients consists of chemotherapy with the medication temozolomide (TMZ), which increases a patient’s life expectancy by approximately two months compared to radiotherapy alone. However, GBM cells can develop resistance to TMZ over time, diminishing its efficacy and increasing the risk of relapse.

In a study published on March 29 in the journal Science Advances, Dr. Xi Huang, a Senior Scientist in the Developmental & Stem Cell Biology program at SickKids, and Dr. Yu Sun, a Professor of Mechanical Engineering and the Director of the Robotics Institute at the University of Toronto, present a new method for treating chemoresistant GBM using precision magnetic control in a technique they call mechanical nanosurgery.

“Using nanotechnology deep within cancer cells, mechanical nanosurgery is a ‘Trojan Horse’ approach that could enable us to eradicate tumor cells from the inside,” says Huang, whose previous research demonstrating that brain tumor cells are mechanosensitive helped to inform the approach. By combining the expertise of biochemists at SickKids and engineers at the University of Toronto, we have developed a prospective new method for treating aggressive brain cancer.

The mouse model used in the study, developed by first author Dr. Xian Wang, Assistant Professor at Queen’s University, former post-doctoral fellow in the Huang Lab, and recipient of a Lap-Chee Tsui Fellowship from the SickKids Research Training Centre, demonstrated that the mechanical nanosurgery process reduced GBM tumor size universally, including in TMZ-resistant GBM.

The workings of mechanical nanosurgery

Magnetic carbon nanotubes (mCNTs) are a type of nanomaterial consisting of carbon nanotubes loaded with iron that become magnetized when exposed to an external magnetic field. In the investigation, mCNTs were coated with an antibody that recognizes a specific protein present on GBM tumor cells. Once injected into a tumor, the antibodies on the mCNTs cause them to seek out and assimilate tumor cells.

“Once the nanotubes are inside the tumor cell, we use a rotating magnetic field to mechanically mobilize the nanotubes in order to stimulate them mechanically,” explains Sun. The force exerted by nanotubes damages cellular structures and leads to the mortality of tumor cells.

Expanding research beyond brain cancer

The partnership between Huang and Sun at the Department of Mechanical Engineering at the University of Toronto continues to build upon the study’s findings. As their research progresses, they observe that mechanical nanosurgery may have additional cancer applications.

Huang explains, “Theoretically, by modifying the antibody coating and rerouting nanotubes to the desired tumor site, we might be able to precisely eliminate tumor cells in other malignancies.”