Summary: Researchers show that silver and zinc oxide nanomaterials can traverse an in vitro blood–brain barrier model as both intact particles and dissolved ions, with their shape and composition influencing passage and potential neurological effects.
Source: University of Birmingham
Metal-based nanomaterials used in consumer and health-care products can move from the blood side to the brain side of an in vitro blood–brain barrier (BBB) model. Their ability to penetrate and the potential for neurological impact depend strongly on particle shape, size, and chemistry, new research shows.
An international team of scientists tested a range of metallic nanoparticles—including silver in several shapes and zinc oxide—using a laboratory model that mimics the tightly packed endothelial cell layer of the BBB. They found that some nanomaterials crossed this barrier either as intact particles or after dissolving into ions, and that certain coatings, shapes, and dissolution behaviors affected how readily they penetrated and how they behaved once beyond the barrier.
The presence of these materials on the brain side of the model was associated with adverse effects on astrocytes, the support cells that regulate many aspects of neuronal health and brain homeostasis. At higher concentrations, and depending on particle morphology, some silver and zinc oxide nanoparticles reduced cell viability and increased barrier permeability—conditions that could allow more substances to enter the brain and raise the risk of neurotoxic outcomes.
While the findings highlight potential health concerns from unintended nanomaterial exposure, the researchers also emphasize the opportunity to exploit these properties for therapeutic purposes. Understanding how physicochemical features govern BBB crossing could inform the design of safer materials and enable targeted delivery strategies for drugs or imaging agents to reach difficult-to-access brain tissues.
Published in PNAS, the study demonstrates that nanoparticle composition, shape, and size determine both penetration efficacy and likely fate in the brain environment. For example, zinc oxide nanoparticles were observed to pass through the model with comparatively greater ease, whereas different silver morphologies—spheres, discs, rods, and wires—showed distinct dissolution behaviors. Some silver particles underwent gradual chemical changes, forming silver–sulfur species within the barrier model that appeared to facilitate further passage.
The blood–brain barrier is essential for protecting the central nervous system. Made up of a compact layer of endothelial cells, it permits oxygen and necessary nutrients to enter the brain while restricting access by many foreign molecules. Disruption of this barrier is associated with increased vulnerability of neural tissue to harmful substances and is implicated in a range of neurological conditions.
Nanomaterials can enter the bloodstream through inhalation, ingestion, or skin contact; a fraction that reaches circulation may encounter the BBB. Prior studies have indicated that certain nanoparticles can accumulate on the brain side in altered chemical states, potentially affecting neuronal signaling and overall brain health. This study adds controlled, comparative evidence that particle geometry and chemistry are critical determinants of whether and how much material crosses an in vitro BBB model and what form it takes after crossing.
To explore these factors systematically, the researchers synthesized a library of metallic nanomaterials varying in composition, size, and shape. Alongside zinc oxide and silver in multiple morphologies, they included cerium oxide and iron oxide nanoparticles for comparison. The team tracked particle fate and dissolution within the model and assessed downstream effects on cells representative of the brain environment, including measures of cell health and barrier integrity.
Co-author Zhiling Guo, a research fellow at the University of Birmingham, noted that mapping how different nanomaterials behave after traversing the BBB is essential to evaluate neurological risk. The study suggests that some materials pose greater neurotoxicity potential than others because their shapes and dissolution pathways enable different transport and accumulation patterns.
Co-author Iseult Lynch, Professor of Environmental Nanosciences at the University of Birmingham, emphasized the dual implications: “Our results show that variations in size, shape, and composition significantly alter nanoparticle interaction with an in vitro blood–brain barrier. These insights are crucial both for assessing potential risks from everyday nanomaterial exposure and for developing deliberately engineered nanoparticles for targeted brain delivery, bioimaging, or therapeutic applications.”
About this blood–brain barrier and nanoscience research news
Source: University of Birmingham
Contact: Tony Moran – University of Birmingham
Image: The image is in the public domain
Original Research: The findings will appear in PNAS