A dense outer layer of polyethylene glycol, or PEG, allows polymeric nanoparticles as large as 114 nm to readily spread through brain tissue (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3003594). The finding, from Justin Hanes and coworkers at Johns Hopkins University, goes against the conventional wisdom that only substances with a diameter of 64 nm or less can move at an appreciable rate through the brain’s extracellular space. The researchers studied how well polymeric nanoparticles of varying sizes and with different surface coatings were able to penetrate human and rat brain tissue samples, as well as mouse brain tissue in vivo. PEG-coated particles with diameters of 114 nm or less diffused easily through the brain tissue, whereas particles with a diameter of 200 nm did not. Particles with a carboxylate coating also failed to penetrate the tissue, regardless of size. The researchers hope their findings will lead to drug delivery systems for treating brain disease. The nanoparticulate treatments are currently limited to direct infusion into the brain, but the researchers speculate they could be delivered intravenously to treat diseases in which the blood-brain barrier is impaired, as it can be with brain tumors, stroke, or neuroinflammation.