Figure 10.

Receptor-mediated transport across the BBB can be facilitated by protein, antibody, peptide, or hormone conjugation to the surface of nanoparticles. a,b) Lactoferrin-functionalized nanoparticles are localized in the brain; whereas, bare nanoparticles do not cross the BBB. TEER values are reduced during the initial exposure to lactoferrin-functionalized nanoparticles but quickly recover and are attributed to measurement fluctuation, suggesting the receptor-mediated crossing of the BBB does not permanently disrupt the barrier function. Reproduced with permission.^[166] Copyright 2012, American Chemical Society. c-e) RVG-targeted nanoparticles accumulate in the hemisphere of the brain with a disrupted BBB. Quantification of nanoparticles in the contralateral (C) and injured hemisphere (I) illustrate significant accumulation when the BBB is disrupted. Astrocytes (GFAP+), microglia (Iba1), and neurons (NeuN) localized at the injury site, where there were reduced astrocytes and microglia after application of the neuron-targeted nanoparticles. Reproduced with permission.^[236] Copyright 2016, American Chemical Society. f-i) PBCA nanoparticles functionalized with APOE across the BBB, but increase DTPA signal intensity is not measured in the brain, suggesting the nanoparticles do not disrupt the BBB. This is further illustrated by an intact BBB, and APOE knockout mice did not display significant uptake of the nanoparticles without the APOE functionalization. Reproduced with permission.^[237] Copyright 2011, National Academy of Science.