期刊
JOURNAL OF CONTROLLED RELEASE
卷 164, 期 1, 页码 49-57出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2012.09.021
关键词
Blood-brain barrier; Magnetic; Drug delivery; Nanoparticles; Image analysis
资金
- Iwama Fund at UC San Diego
- NSF [DMR-1006081]
- NIH [R01-HL073396, R21-ES015871]
- American Brain Tumor Association
- Mechanical and Aerospace Engineering and Bioengineering Departmental Developmental Fund
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1006081] Funding Source: National Science Foundation
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. (C) 2012 Elsevier B.V. All rights reserved.
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