Spatially Precise and Minimally Invasive Delivery of Peptides to the Spinal Cord for Behavior Modulation

The blood–spinal cord barrier (BSCB) tightly regulates the transport of molecules from the blood to the spinal cord. Herein, we present an approach for transient modulation of BSCB permeability and localized delivery of peptides into the spinal cord for behavior modulation with high spatial resolution. This approach utilizes optical stimulation of vasculature-targeted nanoparticles and allows delivery of BSCB-impermeable molecules into the spinal cord without significant glial activation or impact on animal locomotor behavior. We demonstrate minimally invasive light delivery into the spinal cord using an optical fiber and BSCB permeability modulation in the lumbar region. Our method of BSCB modulation allows the delivery of bombesin, a centrally acting and itch-inducing peptide, into the spinal cord and induces a rapid and transient increase in itching behaviors in mice. This minimally invasive approach enables behavior modulation without genetic modifications and is promising for delivering a wide range of biologics into the spinal cord for potential therapy with high spatiotemporal resolution.