Claudin-1-Targeted Nanoparticles for Delivery to Aging-Induced Alterations in the Blood-Brain Barrier

Badrul Alam Bony, Aria W. Tarudji, Hunter A. Miller, Saiprasad Gowrikumar, Sourav Roy, Evan T. Curtis, Connor C. Gee, Alex Vecchio, Punita Dhawan, Forrest M. Kievit

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aging-induced alterations to the blood-brain barrier (BBB) are increasingly being seen as a primary event in chronic progressive neurological disorders that lead to cognitive decline. With the goal of increasing delivery into the brain in hopes of effectively treating these diseases, a large focus has been placed on developing BBB permeable materials. However, these strategies have suffered from a lack of specificity toward regions of disease progression. Here, we report on the development of a nanoparticle (C1C2-NP) that targets regions of increased claudin-1 expression that reduces BBB integrity. Using dynamic contrast enhanced magnetic resonance imaging, we find that C1C2-NP accumulation and retention is significantly increased in brains from 12 month-old mice as compared to nontargeted NPs and brains from 2 month-old mice. Furthermore, we find C1C2-NP accumulation in brain endothelial cells with high claudin-1 expression, suggesting target-specific binding of the NPs, which was validated through fluorescence imaging, in vitro testing, and biophysical analyses. Our results further suggest a role of claudin-1 in reducing BBB integrity during aging and show altered expression of claudin-1 can be actively targeted with NPs. These findings could help develop strategies for longitudinal monitoring of tight junction protein expression changes during aging as well as be used as a delivery strategy for site-specific delivery of therapeutics at these early stages of disease development.

Original languageEnglish (US)
Pages (from-to)18520-18531
Number of pages12
JournalACS Nano
Volume15
Issue number11
DOIs
StatePublished - Nov 23 2021

Keywords

  • C1C2
  • blood-brain barrier
  • fluorescence imaging
  • magnetic resonance imaging
  • nanoparticles
  • tight junctions

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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