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

Research output: Contribution to journalArticlepeer-review

13 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 languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume16
DOIs
StatePublished - 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).

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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