http://www.sciencedirect.com/science/article/pii/S0168365912007092
Abstract
Delivery
of therapeutic or diagnostic agents across an intact blood–brain
barrier (BBB) remains a major challenge. Here we demonstrate in a mouse
model that magnetic nanoparticles (MNPs) can cross the normal BBB when
subjected to an external magnetic field. Following a systemic
administration, an applied external magnetic field mediates the ability
of MNPs to permeate the BBB and accumulate in a perivascular zone of the
brain parenchyma. Direct tracking and localization inside endothelial
cells and in the perivascular extracellular matrix in vivo was
established using fluorescent MNPs. These MNPs were inert and associated
with low toxicity, using a non-invasive reporter for astrogliosis,
biochemical and histological studies. Atomic force microscopy
demonstrated that MNPs were internalized by endothelial cells,
suggesting that trans-cellular trafficking may be a mechanism for the
MNP crossing of the BBB observed. The silica-coated magnetic
nanocapsules (SiMNCs) allow on-demand drug release via remote radio
frequency (RF) magnetic field. Together, these results establish an
effective strategy for regulating the biodistribution of MNPs in the
brain through the application of an external magnetic field.
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