Efficacy of mimetic viral dynein binding peptide binding nanoparticles in blood-brain barrier model

Abstract

The blood-brain barrier (BBB) is a tight barrier that protects stability of the central nervous system (CNS), however, the mechanism impedes the delivery of drugs to the CNS. The interactions between viral proteins and cytoplasmic dynein during infection have been found. In this study, the “linker (dynein binding peptide, DBP)” between virus and dynein was reformed and connected with nanoparticles to try to penetrate the blood-brain barrier. Co-IP and intracellular studies with the designed peptides revealed their interactions with the dynein and their rapid uptake by bEnd.3 cells. And the DBP binding with the cell-penetrating peptide (CPP) exhibited the best intracellular uptake. The peptides were conjucted with DSPE-PEG2000 and prepared to nanoparticles loaded with coumarin-6 (Cou-6). All of the prepared nanoparticles were around 25 nm in size, even though they had different modifications. The 10% DBP-CPP modified coumarin-6-loaded nanocarrier exhibited rapid intracellular distribution and cellular uptake. Transwell studies clearly showed the intercellular transport of the nanoparticles. The study is the first to combine DBP-CPP with a nanodelivery drug carrier and to apply it in a BBB model. The results of our in vitro studies results revealed that DBP can mediate permeation of nanoparticles across the BBB, which may serve as a clinically viable strategy for drug delivery in the brain.