MIT researchers develop nanodevices to kill brain tumor cells

An illustration of HITMAN operating in glioblastoma cells.

An illustration depicts HITMAN nanoantennas being wirelessly activated in glioblastoma tissue. [Image courtesy of Baju Joy and Gopikrishna Pillai]

MIT researchers have developed injectable nanodevices that can be magnetically activated to target and kill brain cancer cells without damaging adjacent healthy tissue.

The MIT Media Lab’s HITMAN (short for highly localized electric field-induced tumor therapy using magnetically actuated nanoantennas) technology employs small nanoantennas to create localized electric fields strong enough to initiate cellular dysfunction, such as damaging cellular membranes or interfering with protein folding, triggering cell death.

“The persistent failure of these therapies underscores the urgent need for novel approaches to target treatment-resistant glioblastoma cells,” the researchers said. “HITMAN offers a minimally invasive, spatially precise, and clinically translatable therapy for glioblastoma.”

The nanoantennas, each about 150 nanometers across, are constructed in two layers. First, a cobalt ferrite core designed to physically react and strain to change shape when hit with a low-frequency magnetic field. The outer layer covers the nanoantennas in a piezoelectric barium titanate shell, which, when squeezed, produces the damaging electric field.

Early laboratory and animal studies showed the technology “significantly reduced tumor growth and extended survival without detectable side effects” against drug-resistant glioblastoma, an aggressive brain cancer with a median survival rate of about 12 to 15 months, MIT Media Lab Chair Deblina Sarkar said.

Using tissue from patients at the Mayo Clinic with aggressive, treatment-resistant glioblastoma, HITMAN eliminated more than half (52%) of drug-resistant cancer cells and left neurons and other healthy cells unharmed.

A figure depicts the magnetically actuated nanoantennas (MANs) and how the technology triggers cell death.

This figure depicts the magnetically actuated nanoantennas (MANs) and how the technology triggers cell death. [Figure courtesy of Monochura Saha, Science Advances]

Then, researchers implanted patient-derived tumor cells in mice to test the technology in vivo. HITMAN inhibited tumor growth and extended median survival in the mice by over 50%. The preclinical experiments showed no systemic toxicity or signs of inflammation, according to the university.

The researchers’ approach delivered therapeutic effects without generating heat or causing other mechanical or chemical effects, suggesting that HITMAN may affect gliomas as they undergo cell division.

The number of distinct cancer cell colonies also declined, from 112 and 150 in the control groups to 26, which the researchers said could translate into reduced tumor recurrence and metastasis.

“Overall, the therapeutic potential of HITMAN, supported by its consistent efficacy in vitro, pronounced antitumor activity in preclinical models and mechanistic clarity, highlights its promise as a compelling candidate for further investigation in translational and clinical settings,” they wrote in a paper published in Science Advances.

While one therapeutic route would involve injecting the nanoantennas directly into the brain, members of the team developed a technology dubbed “circulatronics” that would allow them to be inserted into the bloodstream through the arm, while cloaking them from the body’s immune response and allowing them to pass through the blood-brain barrier.

MIT’s Media Lab and the Nano-Cybernetic Biotrek research group have also been developing comparatively larger injectable antennas, toward the goal of wirelessly powering implants located deep within tissue. Early research showed that designs using low-frequency magnetic fields could generate more power than metallic coils operating in the gigahertz range.