Virus-like Silica Nanoparticles Improve Permeability of Macromolecules across the Blood-Brain Barrier In Vitro

The presence of the blood-brain barrier (BBB) limits the delivery of therapies into the brain. There has been significant interest in overcoming the BBB for the effective delivery of therapies to the brain. Inorganic nanomaterials, especially silica nanoparticles with varying surface chemistry and surface topology, have been recently used as permeation enhancers for oral protein delivery. In this context, nanoparticles with varying sizes and surface chemistries have been employed to overcome this barrier; however, there is no report examining the effect of nanoscale roughness on BBB permeability. This paper reports the influence of nanoscale surface roughness on the integrity and permeability of the BBB in vitro, using smooth surface Stober silica nanoparticles (60 nm) compared to rough surface virus-like silica nanoparticles (VSNP, 60 nm). Our findings reveal that VSNP (1 mg/mL) with virus-mimicking-topology spiky surface have a greater effect on transiently opening endothelial tight junctions of the BBB than the same dose of Stober silica nanoparticles (1 mg/mL) by increasing the FITC-Dextran (70 kDa) permeability 1.9-fold and by decreasing the trans-endothelial electrical resistance (TEER) by 2.7-fold. This proof-of-concept research paves the way for future studies to develop next-generation tailored surface-modified silica nanoparticles, enabling safe and efficient macromolecule transport across the BBB.

Automated summary

This study investigated the effect of nanoscale surface roughness on the integrity and permeability of the blood-brain barrier (BBB). The findings showed that virus-like silica nanoparticles with a spiky surface had a greater impact on the BBB compared to smooth surface silica nanoparticles, resulting in increased permeability and decreased resistance. This research provides a proof-of-concept for the development of surface-modified silica nanoparticles for efficient macromolecule transport across the BBB.