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

Abstract

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.