Neutrophil hitchhiking for nanoparticle delivery to the central nervous system

Neurological diseases are of widespread concern due to high disability and mortality. Nanodrugs have been developed for the treatment of a wide range of neurological disorders, but suffer from problematic delivery to the central nervous system owing to the hindrance of the blood-brain barrier (BBB). In recent advancements, biomimetic nanodrug delivery strategies have emerged as potential solutions to surmount this formidable barrier. Neutrophils are the most abundant white blood cells in humans, playing an essential role in responding to inflammation. Moreover, they possess the capability to traverse impermeable barriers, facilitating the transportation of nanodrugs from the bloodstream into the brain parenchyma. Therefore, neutrophil-mediated nanodrug delivery systems (NM-NDDSs) have shown great potential for neurological disease therapy, as they can prolong the circulation time of nanodrugs, increase their stability and targeting ability, and reduce immunogenicity. In this review, we highlight recent investigations of neutrophils hitchhiking strategies for nanodrug delivery, including intact neutrophils, neutrophil cell membrane-coated drug delivery systems, and neutrophil-derived nanovehicles, and the treatment applications of NM-NDDSs in brain disease. Further investigations are needed to better streamline and standardize the neutrophil-hitchhiking process, which would contribute to a greater enhancement of therapeutic effect and accelerate clinical translation.