Drugs and other treatments can be quite effective at killing cancer cells, yet many fall short as they struggle to penetrate deep into solid tumors due to physical barriers within the tissue. But in a recent study described in ACS Nano, researchers may have found a way to pull them through.
A team of bioengineers at the University of Pennsylvania transported therapeutic nanoparticles, featuring magnetic cores, into the depths of tumors by tugging at them with an external magnetic device. Working in a mouse model of triple-negative breast cancer, the researchers used their approach to slow tumor growth far more than treatment with nanoparticles not exposed to a magnetic field.
“The results are encouraging, particularly because there aren’t many effective treatments for triple-negative breast cancer,” said Tatjana Atanasijevic, Ph.D., a scientific program manager in the Division of Applied Science & Technology at the National Institute of Biomedical Imaging and Bioengineering (NIBIB). “These magnetic particles are excellent drug carriers and imaging enablers and now can also breach a physical blockade that previously seemed impenetrable.”
Chemotherapy and other common forms of cancer treatment attack rapidly dividing cells indiscriminately, sometimes causing serious side effects in otherwise healthy tissue. A longstanding goal of cancer researchers has been to develop strategies that target tumors specifically. One such strategy takes advantage of the leakiness of abnormally formed blood vessels in tumors. Using nanomaterials, researchers can deliver drugs in packages that are big enough to mostly stay out of healthy tissues with intact vasculature but still small enough to slip through the gaps found in tumor vessels.
But while these drug carriers can technically enter tumor tissue, they usually don’t get very far.
“Going this route, you do prevent some uptake from normal tissue, but then the challenge is that the nanoparticles are much bigger than the drugs alone, so they don’t penetrate into the tumor as much. They just get stuck around the blood vessels,” said Andrew Tsourkas, Ph.D., a professor of bioengineering at the University of Pennsylvania and co-lead author of the study.
To help get therapeutics deeper into the dense tissue inside tumors, Tsourkas and his colleagues sought to employ the pulling force of magnetism, which is already used in the clinic routinely. With this approach, nanoparticles would passively leak from the gaps in blood vessels of a tumor and then a magnetic field could spread them more evenly throughout the mass.
In a past study the researchers designed a two-magnet system to pull magnetic iron oxide nanoparticles deeper into tumors in mice. They gained some ground with this approach, propelling the particles further, but the process took eight hours of exposure to the magnetic field. And still, most of the tumor was untouched as the system was only capable of pulling in a single direction.
Building on this research, the team built a cylindrical, eight-magnet system — resembling a miniature magnetic resonance imaging (MRI) machine — that could generate a stronger magnetic field, exerting an outward pull from the center of its opening. They aimed to learn whether the device could achieve better particle penetration and destroy more tumor cells. The authors coated clusters of magnetic nanoparticles with a chemical used in cancer treatments named chlorin e6, or Ce6, which, when struck by certain kinds of light produces reactive molecules, known as free radicals, that are toxic to nearby cells.
The researchers intravenously injected these coated nanoparticle clusters into mice bearing triple-negative breast tumors near the surface of their abdomens and then placed the animals’ midsections in their magnetic device. After three hours, the team used MRI to confirm that the particles, whose magnetic properties make them highly visible with this kind of imaging, accumulated and spread out in tumors far more than in a group where no magnetic field was applied.
Then the researchers shone red lasers through animals’ skin and into breast tumors, activating the Ce6 coatings.
For comparison, another group of mice was treated with the previously developed two-magnet device, while an additional group was not exposed to any magnetic field.
The authors tracked the growth of the tumors over 16 days and then, at the end of the experiment, placed tumors under a microscope to search for the particles. They reported that tumors treated with the new system contained 3.7 times as many particles, which penetrated 3.5 times deeper, compared with tumors treated with the previous device, which ultimately slowed their growth significantly compared to all other groups.
Having achieved their goals of improving therapeutic coverage in tumors, the researchers are now working to learn if they can maintain or improve performance by building larger versions of the magnetic system that are more suitable for humans.
The team also plans to tackle other clinical challenges, where physical barriers in the body make drug targets difficult to access. One application might be using the technology to haul therapeutics through cartilage to treat osteoarthritis.
“There are many applications where poor drug penetration is a major stumbling block, from cancer to joint disease to various lung pathologies. We envision that one day this technology could be broadly useful,” Tsourkas said.
This study was supported in part by grants from NIBIB (R01EB029238 and R01EB028858) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR080820).
This science highlight describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process—each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
Study reference: Bian Jang et al. Enhanced Accumulation and Penetration of Magnetic Nanoclusters in Tumors Using an 8‑Magnet Halbach Array Leads to Improved Cancer Treatment ACS Nano (2025). DOI: https://doi.org/10.1021/acsnano.4c16600