Increased nanoparticle‐loaded exogenous macrophage migration into the brain following PDT‐induced blood–brain barrier disruption

Abstract

Photodynamic therapy (PDT)-induced disruption of the blood-brain barrier (BBB) has been investigated as a technique for the delivery of therapeutic agents to selective regions of the brain. The purpose of this study was to determine the effects of PDT on the migration of systemically administered exogenous macrophages (Ma) loaded with iron oxide nanoparticles in non-tumor bearing rats. A control group consisting of three Sprague-Dawley rats was injected with iron oxide-loaded rat alveolar Ma via jugular vein catheter while two animals were subjected to intracranial injection of iron oxide-loaded Ma. PDT-treated animals were injected with photosensitizer (AlPcS2a ; 1 mg/kg i.p.) followed by light irradiation (wavelength = 670 nm; light dose = 2.5 J) 48 hours later. Light irradiation was performed through the skull. Prior to light irradiation, iron oxide-loaded Ma were administered to each animal. Animals in all groups were imaged in a 7 Tesla (T) magnetic resonance (MR) imager to determine the extent of PDT-induced edema and to evaluate for the presence of iron oxide nanoparticles. Animals were sacrificed 7 days post-Ma administration and their brains analyzed for the presence of iron oxide using Perls staining. Significant uptake of iron oxide nanoparticles by rat alveolar Ma was observed thus providing the rationale for their use as delivery vectors. Histopathological analyses failed to find evidence of iron oxide in normal rat brain. Accumulations of iron oxide-loaded Ma were observed in both MR images and histological sections of non-tumor bearing rat brain following PDT-induced disruption of the BBB. MR imaging was shown to be useful for localizing iron-oxide loaded Ma in rat brains. Exogenous Ma are incapable of traversing the normal BBB and therefore, the use of Ma as delivery vehicles into the brain requires selective disruption of the BBB.