New Research: What Lets Nanoparticles Slip Past the Blood-Brain Barrier?
The blood-brain barrier (BBB) is one of the body's most selective gatekeepers, a dense wall of blood vessel cells, astrocytes, and pericytes that keeps most molecules, pathogens, and particles out of the brain. That's great news for brain health, but a big problem for trying to deliver drugs, and a growing concern for environmental scientists who report finding nanoplastics inside human brain tissue. Somehow, certain nanoparticles are getting through. The question is: which ones, and how?
In a new study published in Advanced Healthcare Materials, our lab collaborated with the George lab at UC Davis set out to answer that question by building a miniature, living model of the human BBB on a chip. Our new platform is a microfluidic BBB, or "mBBB", which lines up the three main BBB cell types side-by-side in a soft, tissue-like matrix and arranges them horizontally so the whole barrier can be watched in real time under a microscope. That optical access is a key upgrade: researchers can now see, not just infer, where a nanoparticle goes and what happens when it gets there.
Using the chip, our team tested three very different classes of nanoparticles against each other: extracellular vesicles (EVs) naturally released by human cells, engineered liposomes of the kind used in modern drug delivery, and polystyrene nanoplastics of the sort found in polluted air, water, and food. Our findings upended some common assumptions. The most efficient brain-crossers by far were the EVs, but not the ones we expected. EVs from a brain-tropic breast cancer line, widely assumed to have special access to the brain, actually trafficked less efficiently than EVs from generic kidney cells. What mattered wasn't where the vesicles came from or how big they were; it was the proteins and lipids decorating their surface. Ligand presentation and membrane composition, not size or stiffness, appear to be critical.
Two other findings stood out. First, even among the best-performing EVs, only about 5-10% made it across with their cargo intact, a sobering reality check for EV-based drug delivery, where intact delivery is the whole point. Second, 100 nm plastic particles barely crossed the barrier at all, yet they still damaged it, punching holes that let other molecules leak through. In other words, a nanoparticle doesn't have to enter the brain to harm it. That decoupling of toxicity from transport is a direct warning for how we think about environmental nanoplastic exposure.
Beyond the specific findings, the mBBB itself is a key deliverable. Because it's built with standard soft lithography and routine cell culture, other labs can reproduce it. Because it's modular, future versions can add neurons, microglia, or disease features. And because it's a human-cell, non-animal system, it fits into the growing push for translational, ethical, and predictive alternatives to animal testing, for both drug discovery and neurotoxicity screening.
The open-access paper, led by Bryan Nguyen, is a collaboration between the Carney Lab and the George Lab in UC Davis Biomedical Engineering.
Link to the manuscript online: A Physiological Microfluidic Blood–Brain-Barrier Model for In Vitro Study of Nanoparticle Trafficking and Accumulation (Adv. Healthcare Mater., 2026)