ANN ARBOR, Mich. — For scientists treating diseases in the brain, crossing the body’s natural barriers to this organ is the most difficult task to complete. Now, scientists at the University of Michigan say nanoparticles are allowing them to break through the nearly impenetrable blood-brain barrier. The achievement is giving cancer researchers the opportunity to deliver a new and game-changing drug to kill brain tumors.
Glioblastoma is the most common and deadliest form of brain cancer in adults. Cases of the illness continue to rise in several countries. The average survival length for patients with glioblastoma is about 18 months. Less than five percent of patients live longer than five years after their diagnosis.
The nanoparticle breakthrough delivers medication intravenously into the patient. These particles, which house the cancer cell-killing drug, are able to slip past the blood-brain barrier and target malignant tumors forming in the brain.
Along with a combination of radiation, the Michigan team says seven of eight mice given this treatment survived their cancers. More importantly, when those seven mice had a recurrence of glioblastoma, their immune systems prevented the cancer from growing back. Each mouse was able to do this without needing further treatments or radiation.
“It’s still a bit of a miracle to us,” says co-senior author Joerg Lahann in a university release. “Where we would expect to see some levels of tumor growth, they just didn’t form when we rechallenged the mice. I’ve worked in this field for more than 10 years and have not seen anything like this.”
Teaching the body how to beat cancer
Researchers say infusing nanoparticles with cancer drugs not only delivered a lethal blow to the main brain tumor, but also helped the patient’s immune system to recognize and attack cancer cells.
“This is a huge step toward clinical implementation,” says study co-author Maria Castro. “This is the first study to demonstrate the ability to deliver therapeutic drugs systemically, or intravenously, that can also cross the blood-brain barrier to reach tumors.”
Castro adds she’s known for five years how she wanted to attack brain cancer, but needed a way to do it. The R.C. Schneider Collegiate Professor of Neurosurgery says her approach stops a specific signal cancer cells broadcast. This signal, STAT3, tricks immune cells into letting cancer inside the patient’s brain.
Castro’s treatment inhibits STAT3, allowing the immune system to eliminate cancer cells which are now exposed to the body’s defenses. The only catch was developing a method to safely get this inhibitor beyond the blood-brain barrier.
How nanoparticles attack brain tumors
Castro consulted with Lahann’s team in the university’s Biointerfaces Institute and began working on a nanoparticle delivery system. Study authors say a protein called human serum albumin is one of the few molecules in blood that successfully crosses the barrier.
The protein became the building block for the new nanoparticles, which utilize synthetic molecules to link the human serum albumins. The team then attached the STAT3 inhibitor and a peptide called iRGD. This compound acts as a tumor homing device for the cancer-killing nanoparticles.
Mice in the initial study received several doses of the nano-prescription over three weeks. The results reveal that mice responding to the treatment saw their survival length jump from 28 days to 41 days. The Michigan team’s second study added radiation therapy to the mix. It’s in this trial where the seven of eight mice made it through and were diagnosed tumor-free.
Researchers are hoping their synthetic protein nanoparticles will soon provide doctors with a new option for destroying currently “undruggable” tumors.
The study appears in the journal Nature Communications.