Brain cancer causes more than 200,000 deaths globally every year. And it’s a hard cancer for doctors to treat. This is because the human brain has a network of blood vessels that prevent harmful substances from reaching it, called the blood-brain barrier.
Although this barrier is meant to protect the brain, it also prevents chemotherapy treatment in the blood from getting to the brain and reaching brain cancer. As the cancer grows, this barrier becomes more permeable, or “leaky”, and allows more substances to enter the brain.
Scientists have tested a new approach to treat brain cancer, by taking advantage of this increased “leakiness” of the blood-brain barrier. This branch of medicine uses very small molecules to deliver substances to living tissues, and is called nanomedicine. With brain cancer, doctors have developed nanomedicine approaches using a type of molecule called a polymer to deliver chemotherapy to the tumor site.
In previous studies of brain cancer, scientists tested a nanomedicine called doxorubicin, or Dox for short. It was effective in reducing the size of brain tumors in mice, but caused heart damage when used by itself. The scientists hypothesized they could more safely deliver Dox to the tumor site by attaching it to a polymer.
Last year, researchers from the University of Queensland studied the effectiveness of Dox-polymer nanomedicine in mice that had genes favorable for cancer growth. The researchers injected a hormone into the mice to delete genes that prevent cancer growth. Their goal was to induce the growth of brain tumors in the mice, which would lead to a more permeable blood-brain barrier with better access for nanomedicine treatment.
The researchers monitored the mice’s brains weekly for tumor growth using magnetic resonance imaging, what doctors call an MRI. Once they detected brain tumors, they injected a contrast agent into the mice and observed when the substance began to leak from the blood vessels.
Tumor blood vessels are more leaky than healthy blood vessels, with larger pores that allow for the treatment to enter and target the tumor tissue. Therefore, by monitoring the blood vessel “leakiness”, the researchers could determine the optimal time to deliver the nanomedicine treatment. They reasoned since the blood-brain barrier was the most permeable for each mouse at a different time, the treatment was unique for each mouse.
The researchers separated the mice into four groups that each received different treatments. One group received Dox with a polymer delivery system, one received Dox without a polymer, one received Dox with both a polymer and an anti-cancer antibody attached to it, and one received no treatment. The team gave the treatments to mice with both early-stage and late-stage tumors, which they identified ahead of time.
The researchers chose a polymer that had been shown previously to carry Dox to the tumor tissue with minimal side effects. Once at the blood-brain barrier, Dox targeted an area that is highly specific for certain substances, called a receptor. The receptor acted like a locked gate that will only open with a specific key.
The researchers included anti-cancer antibodies in one of the treatments. These antibodies acted as the key to open the receptor gate, allowing Dox to pass through the blood-brain barrier and target the tumor tissue. Then they collected both brain and cardiovascular tissue from the mice to study the effects of each treatment on their brains and hearts.
The researchers observed steady but slow growth in late stage tumors, and very little growth in early stage tumors, in mice that received Dox treatment with both the polymer and the antibodies. The researchers also found slower tumor growth, more dead tumor cells, and less heart damage in mice treated with both a polymer and Dox. They interpreted this data to mean the nanomedicine treatment had fewer harmful side effects than Dox alone.
The team suggested this mouse population was representative of a human population suffering from brain tumors, since the disease progression was different for each mouse. The scientists think this new personalized nanomedicine approach could improve a brain cancer patient’s quality of life by slowing their cancer progression and reducing the side effects of heart damage. They indicated their research adds to a growing body of literature showing how chemotherapy delivered via nanomedicine can provide a safe and effective treatment for cancer patients.