TY  - JOUR
AU  - Moscariello, Pierpaolo
AU  - Ng, David Y W
AU  - Jansen, Malin
AU  - Weil, Tanja
AU  - Luhmann, Heiko J
AU  - Hedrich, Jana
TI  - Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates.
JO  - Advanced science
VL  - 5
IS  - 5
SN  - 2198-3844
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2018-01205
SP  - 1700897
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29876217
C2  - pmc:PMC5979778
DO  - DOI:10.1002/advs.201700897
UR  - https://inrepo02.dkfz.de/record/136767
ER  -