Abstract: The blood-brain barrier (BBB) excludes most drugs and poses a significant challenge to treat brain diseases. Current methods for BBB opening yield modest outcomes in clinical applications due to safety and toxicity. This disclosure relates to methods of optically opening the BBB by laser excitation of tight-junction targeted nanoparticles to induce BBB transient opening. The excitation of plasmonic nanoparticles produces localized effects such as nanoscale heating and photomechanical force leading to BBB transiently opening to allow macromolecules across it. The safe and predictable platform for brain drug delivery will improve therapies for brain disease such as cancers, infections and neurologic disorders.