Abstract
This study constructed an in vitro blood-brain barrier (BBB) transwell model to investigate the regulatory effects and mechanisms of the photothermal effects of gold nanorods (AuNRs) excited by the second near-infrared region (NIR-II) on BBB permeability. The experimental results showed that the photothermal effects of NIR-II + AuNRs significantly decreased trans-epithelial electrical resistance (TEER) and increased the permeability of fluorescein isothiocyanate (FITC)-dextran, indicating that it can effectively open the BBB. This effect was reversible, and the TEER and FITC permeability returned to baseline levels within 24 h after treatment. Mechanistic studies revealed that BBB opening did not rely on apoptosis, cytoskeletal disruption, mitochondrial dysfunction, or inflammation. The opening of the BBB was closely associated with a temporary decrease in the expression and conformational change of the tight junction protein occludin due to the photothermal effect. Molecular simulations and docking analysis revealed that the heat shock protein HSP70 could bind to the conformationally altered occludin, supporting the regulatory role of photothermal effects on tight junction proteins. In summary, NIR-II + AuNRs achieved safe and reversible opening of the BBB by regulating the conformation and expression of tight junction proteins, providing a deeper insight for further research on BBB and the treatment of neurological diseases.