TY - JOUR
T1 - Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain
AU - Ahlschwede, Kristen M.
AU - Curran, Geoffry L.
AU - Rosenberg, Jens T.
AU - Grant, Samuel C.
AU - Sarkar, Gobinda
AU - Jenkins, Robert B.
AU - Ramakrishnan, Subramanian
AU - Poduslo, Joseph F.
AU - Kandimalla, Karunya K.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/2
Y1 - 2019/2
N2 - Accumulation of amyloid beta (Aβ) peptides in the cerebral vasculature, referred to as cerebral amyloid angiopathy (CAA), is widely observed in Alzheimer's disease (AD) brain and was shown to accelerate cognitive decline. There is no effective method for detecting cerebrovascular amyloid (CVA) and treat CAA. The targeted nanoparticles developed in this study effectively migrated from the blood flow to the vascular endothelium as determined by using quartz crystal microbalance with dissipation monitoring (QCM-D) technology. We also improved the stability, and blood–brain barrier (BBB) transcytosis of targeted nanoparticles by coating them with a cationic BBB penetrating peptide (K16ApoE). The K16ApoE-Targeted nanoparticles demonstrated specific targeting of vasculotropic DutchAβ40 peptide accumulated in the cerebral vasculature. Moreover, K16ApoE-Targeted nanoparticles demonstrated significantly greater uptake into brain and provided specific MRI contrast to detect brain amyloid plaques.
AB - Accumulation of amyloid beta (Aβ) peptides in the cerebral vasculature, referred to as cerebral amyloid angiopathy (CAA), is widely observed in Alzheimer's disease (AD) brain and was shown to accelerate cognitive decline. There is no effective method for detecting cerebrovascular amyloid (CVA) and treat CAA. The targeted nanoparticles developed in this study effectively migrated from the blood flow to the vascular endothelium as determined by using quartz crystal microbalance with dissipation monitoring (QCM-D) technology. We also improved the stability, and blood–brain barrier (BBB) transcytosis of targeted nanoparticles by coating them with a cationic BBB penetrating peptide (K16ApoE). The K16ApoE-Targeted nanoparticles demonstrated specific targeting of vasculotropic DutchAβ40 peptide accumulated in the cerebral vasculature. Moreover, K16ApoE-Targeted nanoparticles demonstrated significantly greater uptake into brain and provided specific MRI contrast to detect brain amyloid plaques.
KW - Alzheimer's disease (AD)
KW - BBB permeating peptide
KW - Cerebrovascular amyloid
KW - Magnetic resonance imaging (MRI)
KW - Targeted nanoparticles
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UR - http://www.scopus.com/inward/citedby.url?scp=85058220814&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2018.09.010
DO - 10.1016/j.nano.2018.09.010
M3 - Article
C2 - 30300748
AN - SCOPUS:85058220814
SN - 1549-9634
VL - 16
SP - 258
EP - 266
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
ER -