Magnetic targeting of nanoparticles across the intact blood-brain barrier.
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.
Materials Science & Engineering, UC San Diego, La Jolla, CA 92093, USA.
Seong Deok
SD
Kong
Jisook
J
Lee
Srinivasan
S
Ramachandran
Brian P
BP
Eliceiri
Veronica I
VI
Shubayev
Ratnesh
R
Lal
Sungho
S
Jin
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D049409:Luciferases, Firefly / Q000235:genetics; D008163:Luminescent Measurements; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution; D050781:Transcranial Magnetic Stimulation
D004337:Drug Carriers; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D049409:Luciferases, Firefly; D007052:Ibuprofen