| Autor: |
Kucharz K; Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark. kucharz@sund.ku.dk., Kristensen K; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Johnsen KB; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Lund MA; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Lønstrup M; Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark., Moos T; Department of Health Science and Technology, Aalborg University, Aalborg Ø, Denmark., Andresen TL; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Lauritzen MJ; Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark. mlauritz@sund.ku.dk.; Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark. mlauritz@sund.ku.dk. |
| Abstrakt: |
Effective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo. We show that transferrin receptor-targeted liposome nanoparticles are sequestered by the endothelium at capillaries and venules, but not at arterioles. The nanoparticles move unobstructed within endothelium, but transcytosis-mediated brain entry occurs mainly at post-capillary venules, and is negligible in capillaries. The vascular location of nanoparticle brain entry corresponds to the presence of perivascular space, which facilitates nanoparticle movement after transcytosis. Thus, post-capillary venules are the point-of-least resistance at the BBB, and compared to capillaries, provide a more feasible route for nanoparticle drug carriers into the brain. |
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