Uptake of systemically administered magnetic nanoparticles (MNPs) in areas of experimental spinal cord injury (SCI)

Abstract

The regenerative potential of the adult central nervous system (CNS) is limited, contributing to poor recovery from neurological insult. Many genes have been identified that promote neural regeneration, but the current viral methods used to mediate neural gene transfer have a range of drawbacks, notably safety. Non-viral magnetic nanoparticle (MNP)-based vector systems offer significant advantages over viral systems, including: (a) safety; (b) flexibility of functionalization with genetic material; (c) potential for non-invasive magnetic targeting; and (d) imaging potential. The applications of such a system to promote intrinsic neural regeneration have not been assessed. We examined uptake of intravenously administered MNPs (diameter, 320 nm) into areas of experimental rodent spinal cord injury (SCI), using a transection model. We found focal uptake of MNPs in areas of SCI associated with breakdown of the blood-brain barrier (BBB) within 6 h of injury; a spatial association was observed between MNPs and nuclei in lesions, suggesting that particle uptake was occurring in cells within injury sites. Our data suggest that there may be a 'therapeutic window of opportunity' during post-injury BBB compromise within which MNPs can be used to mediate gene transfer to sites of spinal cord trauma. Taking into account the relatively superficial anatomical location of the spinal cord, these findings also raise the possibility that the spinal cord could be an attractive target for MNP-based delivery of biomolecules, particularly when combined with magnetic targeting strategies. We discuss factors that will need to be addressed in order to optimize such an approach.