Journal Article

DKFZ-2018-01205

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates.

Moscariello, P. ; Ng, D. Y. W. ; Jansen, M.DKFZ* ; Weil, T. ; Luhmann, H. J. ; Hedrich, J.

2018
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/advs.201700897

Abstract: Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood-brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pathway and transported across the BBB via transcytosis escaping from lysosomes. After transcytosis DSA are delivered to astrocytes and neurons. Furthermore, DSA offer high biocompatibility in vitro and in vivo. In summary, a new strategy for implementing therapeutic PAMAM function as well as drug delivery in neuropathology is presented here.

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Contributing Institute(s):

1. Molekulare Neurogenetik (A240)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2018

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Database coverage:
; ; ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 5 ; JCR ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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