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 Brian Jenkins, Subramanian Ramakrishnan, Joseph F. Poduslo, Karunya K. Kandimalla

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
JournalNanomedicine: Nanotechnology, Biology, and Medicine
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Amyloid
Nanoparticles
Peptides
Brain
Alzheimer Disease
Cerebral Amyloid Angiopathy
Quartz Crystal Microbalance Techniques
Transcytosis
Amyloid beta-Peptides
Amyloid Plaques
Vascular Endothelium
Quartz crystal microbalances
Magnetic resonance imaging
Technology
Blood
Coatings
Monitoring

Keywords

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

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain. / Ahlschwede, Kristen M.; Curran, Geoffry L.; Rosenberg, Jens T.; Grant, Samuel C.; Sarkar, Gobinda; Jenkins, Robert Brian; Ramakrishnan, Subramanian; Poduslo, Joseph F.; Kandimalla, Karunya K.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, 01.01.2018.

Research output: Contribution to journalArticle

Ahlschwede, Kristen M. ; Curran, Geoffry L. ; Rosenberg, Jens T. ; Grant, Samuel C. ; Sarkar, Gobinda ; Jenkins, Robert Brian ; Ramakrishnan, Subramanian ; Poduslo, Joseph F. ; Kandimalla, Karunya K. / Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2018.
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AU - Jenkins, Robert Brian

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