Editors' ChoiceNanotechnology

More than Just “Getting In”

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Science Translational Medicine  28 Sep 2011:
Vol. 3, Issue 102, pp. 102ec159
DOI: 10.1126/scitranslmed.3003238

One often sees “University Alumni” bumper stickers on cars. Apparently, it is now possible to attach a “Former Student” sticker to your car, instead, thus implying that attendance—but not graduation—occurred at that university. Gaining admission to college is commendable; nevertheless, most parents have the hope that students will strive to do more than just “get in.” In other words, they should complete their degrees.

Similarly, delivering therapeutics across the blood-brain barrier (BBB) is not an easy task, although several promising strategies have emerged to increase the uptake of drug-loaded nanoparticles into the brain. Huile et al. have gone beyond simply getting into the brain: after crossing the BBB, their designer particles target a specific cell type called glia. The authors first modified the surfaces of polymeric nanoparticles with both a peptide (angiopep-2) and a protein (EGFP-EGF1) as part of a “cascade” targeting strategy. Angiopep-2 promoted penetration across the BBB, whereas EGFP-EGF1 showed high affinity for thromboplastin, which is highly expressed in glial cells in the brain. After in vitro experiments corroborating the dual-targeting strategy, nanoparticles were given to rats. Ex vivo imaging, fluorescent in situ hybridization, and transmission electron microscopy experiments all demonstrated that these nanoparticles crossed the BBB and reached their glial cell targets.

Huile and colleagues suggest that this cascade targeting approach will enhance drug treatment by reducing side effects in nontarget regions of the brain. Furthermore, because glia are involved in several diseases of the central nervous system such as Alzheimer’s, stroke, and epilepsy, these cell-specific nanoparticles are therapeutically versatile. This nanoparticle design goes beyond “just getting in” and aims to accomplish the laudable goal of treating aberrant brain cells in neurodegenerative diseases.

G. Huile et al., A cascade targeting strategy for brain neuroglial cells employing nanoparticles modified with angiopep-2 peptide and EGFP-EGF1 protein. Biomaterials 32, 8669–8675 (2011). [Abstract]

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