Spatially\nPrecise and Minimally Invasive Delivery\nof Peptides to the Spinal Cord for Behavior Modulation

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