Bacteriophage carriers localize in the brain of a rat model of neonatal hypoxic‐ischemic encephalopathy

Background Neonatal hypoxic‐ischemic encephalopathy arises from a reduction of oxygen and blood supply to the infant brain and can lead to severe brain damage and life‐long disability. The damage is greatest at the irreversibly injured necrotic core, whereas the penumbra is the surrounding, potentially salvageable tissue populated with a mix of alive and dying cells. To date, there exists no method for targeting drugs to the brain damage. Methods and Major Results Bacteriophages are viruses that propagate in bacteria but are biocompatible in humans and also amenable to genetic and chemical modification in a manner distinctive from conventional therapeutic nanoparticles. Here, a library of M13 bacteriophage was administered into a rat model of hypoxic‐ischemic encephalopathy, and unique bacteriophage clones were confirmed to localize in healthy brain tissue versus the core and penumbra zones of injury. Conclusions For the first time, there is a potential to directly deliver therapeutics to different regions of the neonatal brain injury. Graphical and Lay Summary A library of M13 bacteriophage tagged with unique 12‐mer peptide sequences on the order of 109 diversity was injected into newborn rats following the induction of hypoxic‐ischemic brain injury. After three iterations of bacteriophage recovery from the injured site of the cerebral cortex, re‐injection into the animal model, and DNA sequencing, we identified the enrichment of specific bacteriophage clones in the lesion .