Abstract: Inhibition of EphB receptors (e.g., EphB1) can be used in therapeutic methods for treating EphB receptor-associated conditions (e.g., pain, cancer). Demeclocycline, chlortetracycline, and minocycline are identified as EphB receptor inhibitors. Accordingly, aspects of the disclosure relate to methods for treating pain comprising providing demeclocycline, chlortetracycline, minocycline, or derivatives thereof, alone or in combination, to an individual in need thereof. Further aspects relate to pharmaceutical compositions comprising two or more of minocycline, demeclocycline, chlortetracycline, and/or derivatives thereof.

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.