Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain

Kristen M. Ahlschwede; Geoffry L. Curran; Jens T. Rosenberg; Samuel C. Grant; Gobinda Sarkar; Robert B. Jenkins; Subramanian Ramakrishnan; Joseph F. Poduslo; Karunya K. Kandimalla

doi:10.1016/j.nano.2018.09.010

Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain

Kristen M. Ahlschwede, Geoffry L. Curran, Jens T. Rosenberg, Samuel C. Grant, Gobinda Sarkar, Robert B. Jenkins, Subramanian Ramakrishnan, Joseph F. Poduslo, Karunya K. Kandimalla

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	258-266
Number of pages	9
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	16
DOIs	https://doi.org/10.1016/j.nano.2018.09.010
State	Published - Feb 2019

Bibliographical note

Funding Information:
Funding: This work was supported by the Minnesota Partnership for Biotechnology and Medical Genomics grant (KKK and JFP). A portion of this work was performed at the National High Magnetic Field Laboratory which was supported by the State of Florida and the National Science Foundation (DMR-1157490 and DMR-1644779). Further, National Science Foundation (NSF) is acknowledged for funding a portion of this work (SR 1735968).

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

Alzheimer's disease (AD)
BBB permeating peptide
Cerebrovascular amyloid
Magnetic resonance imaging (MRI)
Targeted nanoparticles

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.nano.2018.09.010

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Ahlschwede, K. M., Curran, G. L., Rosenberg, J. T., Grant, S. C., Sarkar, G., Jenkins, R. B., Ramakrishnan, S., Poduslo, J. F., & Kandimalla, K. K. (2019). Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain. Nanomedicine: Nanotechnology, Biology, and Medicine, 16, 258-266. https://doi.org/10.1016/j.nano.2018.09.010

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abstract = "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.",

keywords = "Alzheimer's disease (AD), BBB permeating peptide, Cerebrovascular amyloid, Magnetic resonance imaging (MRI), Targeted nanoparticles",

author = "Ahlschwede, {Kristen M.} and Curran, {Geoffry L.} and Rosenberg, {Jens T.} and Grant, {Samuel C.} and Gobinda Sarkar and Jenkins, {Robert B.} and Subramanian Ramakrishnan and Poduslo, {Joseph F.} and Kandimalla, {Karunya K.}",

note = "Funding Information: Funding: This work was supported by the Minnesota Partnership for Biotechnology and Medical Genomics grant (KKK and JFP). A portion of this work was performed at the National High Magnetic Field Laboratory which was supported by the State of Florida and the National Science Foundation (DMR-1157490 and DMR-1644779). Further, National Science Foundation (NSF) is acknowledged for funding a portion of this work (SR 1735968). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

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AU - Poduslo, Joseph F.

AU - Kandimalla, Karunya K.

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PY - 2019/2

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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.

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Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain

Abstract

Bibliographical note

Keywords

UN SDGs

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