For patients with late-stage cancer, treatment often involves enduring multiple types of therapy, such as chemotherapy, surgery, and radiation.
This can cause severe side effects and doesn’t always lead to successful outcomes.
In hopes of improving treatment options, researchers at MIT have developed tiny particles that can be implanted at a tumor site to deliver two types of therapy at once: heat and chemotherapy.
This new approach not only reduces the side effects of traditional chemotherapy, which is usually given through the veins, but also offers a combined effect that may extend a patient’s life.
In a study on mice, this dual therapy completely eliminated tumors in most cases and significantly increased the animals’ survival.
“One area where this technology could be particularly helpful is in managing fast-growing tumors,” says Ana Jaklenec, a senior researcher at MIT’s Koch Institute for Integrative Cancer Research.
“Our goal is to provide some control over these tumors, potentially extending the patient’s life or at least improving their quality of life.”
Jaklenec co-authored the study with Angela Belcher, Professor of Biological Engineering and Materials Science at MIT, and Robert Langer, an MIT Institute Professor.
The study’s lead author is Maria Kanelli, a former postdoctoral researcher at MIT. Their findings were recently published in the journal ACS Nano.
In addition to chemotherapy, the team wanted to incorporate phototherapy, a treatment that uses light to kill cancer cells.
Phototherapy works by implanting or injecting particles that can be heated with an external laser. This raises the temperature of the particles enough to destroy nearby tumor cells without harming surrounding tissues.
The researchers chose molybdenum disulfide as the phototherapy agent because it efficiently converts laser light into heat. This material allows for the use of lower-powered lasers, which are safer for patients.
To create microparticles that could deliver both therapies, the team combined molybdenum disulfide nanosheets with chemotherapy drugs, either doxorubicin (a water-loving drug) or violacein (a water-repelling drug).
They then mixed these ingredients with a biocompatible polymer called polycaprolactone. The mixture was dried into a film and pressed into tiny particles measuring about 200 micrometers wide.
When these particles are injected into a tumor, they stay in place. An external laser can then be used to heat the particles during each treatment session. This heat can penetrate up to a few centimeters into the tissue, targeting the tumor directly.
“The advantage of this platform is that you only need to inject it once,” Kanelli explains. “Then, you can use a laser to release the drug and simultaneously heat up the particles to kill the cancer cells.”
The researchers used machine-learning algorithms to determine the best settings for the laser treatment, including the power level, duration, and concentration of the phototherapy agent. They designed a treatment cycle that lasts about three minutes, during which the particles are heated to 50 degrees Celsius. This temperature is hot enough to kill cancer cells while also melting the polymer, which releases the chemotherapy drug into the tumor.
“This optimized laser system lets us deliver low-dose chemotherapy locally, using the deep penetration ability of near-infrared light,” says Neelkanth Bardhan, a co-author of the study. “This combined effect reduces the harmful side effects that are common with traditional chemotherapy.”
In tests on mice with aggressive cancer cells, the researchers implanted around 25 microparticles per tumor and performed three laser treatments, with three days between each session. The tumors in these mice were completely eradicated, and they lived much longer than mice that received only one type of treatment or no treatment at all.
“The ability to control drug release with light, after just one dose of particles, is a major breakthrough,” says Belcher. “It could make treatment less painful and improve patient compliance.”
The polymer used for these particles is already approved by the FDA for medical devices, which makes it promising for further development. The researchers hope to test this approach on larger animals next and eventually move to clinical trials. They believe this method could be useful for treating all types of solid tumors, including those that have spread.
By combining heat and chemotherapy in one treatment, this innovative technology offers hope for more effective cancer therapies with fewer side effects, giving patients a better chance at a longer and higher-quality life.
