Monitoring Subtle Changes of Blood–Brain Barrier Permeability via Detection of MiRNA-155 in Brain Microvasculature

Abstract

The changes of blood–brain barrier (BBB) permeability need to be sensitively reported when purposefully regulating the BBB or during some brain diseases. Currently available techniques for assessment of BBB integrity all suffer from limited sensitivity and only report serious BBB damage. Here, a targeted activatable nanoprobe is created to monitor subtle changes of BBB permeability by detecting the expression levels of BBB permeability-related miRNA (miRNA-155) in brain microvessel endothelial cells (BMECs). The probe is fabricated by coating the BMEC membrane on calcium phosphate (CaP)-mineralized metal-organic framework (MOF) nanoparticles loaded with hybridization chain reaction (HCR) probes. The coating of the BMEC membrane endows the nanoprobe with homologous targeting ability to BBB, and HCR probes released and escaped from lysosomes can be specifically lightened by miRNA-155. The activatable nanoprobe is able to monitor BBB permeability in inflammatory and AD mice. This work provides a new idea for highly sensitive evaluation of the BBB permeability, which has guiding significance in regulating BBB and formulating targeted therapeutic strategies.