Houston Methodist scientists have created a first-of-its-kind method to deliver medicine to neural cells, a promising new avenue for treating brain disease and injury.

Using a combination of synthetic and biological materials, the team developed nanometer-scale vehicles — known as humanized biomimetic nanovesicles — capable of transporting therapeutics that promote the regeneration needed to reverse or repair ongoing damage in conditions ranging from neurodegenerative disease and stroke to brain trauma.

"By combining our distinctive technologies, we've invented a new delivery system to brain cells," said Robert Krencik, a Houston Methodist professor of neurosurgery in the Center for Neuroregeneration and the lead author of a new paper on the research. "It has promise for safer, more targeted delivery."

Krencik noted that the novel delivery system also should enable improved diagnosis of brain trauma and degeneration by shuttling sensors to damaged sites.

The Houston Methodist research is described in the Aug. 11, 2021 issue of the journal Advanced Science.

A technology able to target neural cells

Nanovesicles able to target neural cells would constitute a major advance. Currently, medicine's ability to heal damage after traumatic brain injury or neural degeneration is hindered by a lack of effective technologies capable of transporting drugs precisely where they're needed.

To solve the problem, Krencik's team used induced pluripotent stem cells (iPSCs) as a source of biological material to develop the biomimetic humanized neural nanovesicles, which can carry cargo such as medication, mRNA or diagnostic material.

Nanoscale transport systems have become valuable medical tools in recent years, functioning as carriers for the transfer of drugs and genes and as contrast agents in imaging. 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.

Still, research in neural conditions has lagged far behind. Francesca Taraballi, a Houston Methodist professor of orthopedics and translational biomaterials and a co-author on the Advanced Science paper, earlier this year published some of the first such neural research when her team showed its nanoparticle transport system crossed the blood-brain barrier in mice and delivered drugs that reduced brain lesions.

In the new research, the Houston Methodist team coded specific cell membrane-derived proteins onto lipid-based nanovesicles, a kind of masquerade that characterizes biomimicry. The protein-encoded nanovesicles are recognized and taken in by neural cells, which then distribute their cargo.

Nanovesicles tested on "mini-brain" neural organoids

Delivery to specifically targeted cells and not others is the goal because it would prevent side effects.

The team tested the nanovesicles on neural organoids, 3D brain-like structures that show organized waves of activity similar to those found in human brains. The organoids, often called "mini-brains" by the popular media, allow researchers to carry out experiments not possible in people. This research marks the first time scientists have shown that human neural organoids can be used as a nanomedicine testing platform.

Taraballi and Krencik envision the technology being applied to other conditions like cancers, particularly glioblastoma, for which current treatment only extends life a short time. That will be the focus of future research.

"The main result of this study is that we generated and validated a new class of drug delivery system, specifically formulated to target brain cells," says Krencik. "A future direction is to test whether we can design them for improved targeting to other cell types as well."

The first priorities are Alzheimer's and Parkinson's diseases. Krencik said he hopes to have preclinical trials up and running within a few years.

The Houston Methodist team collaborated on the project with researchers at MD Anderson Cancer Center and Technion-Israel Institute of Technology.