Engineered Protein Coronas Reveal That Apolipoprotein E Enhances Transport of Particulate Pollutants across the Blood-Brain Barrier

Ultrafine and nanoscale particulate matter (PM) is increasingly implicated in adverse neurological outcomes, yet the molecular mechanisms governing its interaction with blood proteins and transport across the blood-brain barrier (BBB) remain unclear. Here, we establish an engineered protein-corona model to dissect how blood-borne particles acquire BBB-relevant transport properties. Gold nanoparticles were used as a controlled surrogate for PM and functionalized with thiolated DNA aptamers to enable reproducible assembly of defined coronas composed of three physiologically relevant proteinshuman serum albumin (HSA), apolipoprotein E (ApoE), and complement component C3b. In a bEnd.3 Transwell BBB model, corona identity dictated enhanced colloidal stability and transcytosis efficiency, with ApoE-enriched coronas nearly doubling apparent permeability and increasing 24 h transport by 1.6-fold relative to bare particles. Mechanistic studies revealed an energy-dependent, predominantly clathrin-mediated uptake pathway. Importantly, ApoE precoronation also enhanced endothelial penetration of polystyrene particles and increased the endothelial cytotoxicity of diverse industrial-source PM samples. This work provides a mechanistic framework linking protein corona composition to BBB penetration, advancing molecular risk assessment of environmentally relevant particulate matter.