Claudin-1-Targeted Nanoparticles for Delivery to Aging-Induced Alterations in the Blood–Brain Barrier
| Autor: | Aria W. Tarudji, Evan T. Curtis, Saiprasad Gowrikumar, Punita Dhawan, Badrul Alam Bony, Sourav Roy, Hunter A. Miller, Forrest M. Kievit, Alex J. Vecchio, Connor C. Gee |
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| Rok vydání: | 2021 |
| Předmět: |
Aging
Fluorescence-lifetime imaging microscopy medicine.diagnostic_test Tight junction Chemistry General Engineering Endothelial Cells General Physics and Astronomy Magnetic resonance imaging Primary event Blood–brain barrier Article Tight Junctions Mice medicine.anatomical_structure Targeted nanoparticles Blood-Brain Barrier Claudin-1 medicine Cancer research Animals Nanoparticles General Materials Science Cognitive decline Claudin |
| Zdroj: | ACS Nano |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.1c08432 |
| Popis: | 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 lack of specificity towards 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 (DCE-MRI) we find that C1C2-NP accumulation and retention is significantly increased in brains from 12-month-old mice as compared to non-targeted 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. |
| Databáze: | OpenAIRE |
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