Nanoparticles can be targeted to injured brains, according to a Houston Methodist mouse study, a finding that bodes well for better diagnosis and treatment of the hard-to-reach organ.

The study showed that a novel nanoparticle delivery system developed by the team crosses the blood-brain barrier, where it can be used to recognize disease states and reduce inflammation. Such a delivery system is needed because most drugs can't penetrate the barrier.

"These results suggest nanoparticles represent a promising future theranostic tool for traumatic brain injury (TBI)," says Sonia Villapol, a Houston Methodist Research Institute neuroscientist and the study's co-primary investigator. "They can lead the revolution to make the field more sophisticated and precise."

The study, published this spring in the journal Advanced Functional Materials, focuses on traumatic brain injury, for which there is no effective pharmacotherapy. The team next plans to test the delivery system on Alzheimer's disease, which also lacks effective treatment and is characterized by inflammation.

An emerging tool still in the early stages of brain application

The research is still far from being ready to test in people, says Villapol.

Nanoparticles, materials far smaller than what the human eye can detect, have become valuable medical tools in recent years, able to function as contrast agents in imaging and as carriers for the delivery of drugs and genes. Most of the application has come in cancer, but the technology's use in COVID-19 vaccines has increased general research in the field exponentially, says Francesca Taraballi, a Houston Methodist professor of orthopedics and translational biomaterials and the study's other co-primary investigator.

Still, nanoparticle research in brain injury lags behind. The Advanced Functional Materials paper is one of the first to show the technology's promise for the organ.

Few areas of disease are more in need of improved treatment. Immediately following brain injury, a neuroinflammatory cascade triggers brain degeneration that can cause hematoma, subarachnoid hemorrhage and axonal injury. Most have long-term physical, emotional and cognitive consequences.

A serious and growing health problem in the U.S., TBI annually accounts for 2.5 million emergency room visits, 56,000 deaths and more than $60 billion in direct medical expenses for palliative care and cognitive rehabilitation.

Brain drug treatment's big obstacle: crossing the blood brain barrier

Historically, drugs that might help prevent neurodegeneration are hard to deliver to brain tissue because of the blood brain barrier — a dense wall of cells that allows in oxygen, water and other vital substances but that prevents larger materials circulating in the blood from entering. Because they're ultra-small, nanoparticles have been seen as good candidates to breach the barrier.

In mouse models, Villapol and Taraballi showed that leukocyte-based biomimetic nanoparticles accessed the brain's inflamed regions and delivered anti-inflammatory drugs that decreased macrophage infiltration and brain lesions, compared to sham vehicle-treated mice.

The delivery system was visualized using advanced in vivo imaging techniques.

"Our results demonstrated that biomimetic nanoparticles could be strong candidates for acute pharmacologic treatment in TBI patients," Villapol and Taraballi write in the paper. "By observing the infiltration of nanoparticles into inflamed tissues, we can now design how to overcome the therapeutic challenges of TBI using pharmacological therapy targeting specific inflammatory mechanisms."