Biocompatible Red Fluorescent Organic Nanoparticles with Tunable Size and Aggregation-Induced Emission for Evaluation of Blood-Brain Barrier Damage

Abstract

A fluorescence imaging method, based on 2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)-phenyl)fumaronitrile (TPETPAFN) nanoparticles (NPs) that could achieve sensitive and specific detection of blood-brain barrier (BBB) patency was studied. Modified nanoprecipitation method was applied to fabricate TPETPAFN NPs with controlled sizes. In a rat photothrombotic ischemia (PTI) model, the TPETPAFN NPs demonstrate the capacity for sensitive and specific monitoring of the BBB integrity. In vivo studies reveal that NPs with sizes greater than 30 nm do not extravasate, while NPs with the size of 10 nm could leak from nonischemic regions of the brain in the PTI model, although none of the NPs leak from the healthy brains. As a consequence, the 30 nm NPs could provide clear evaluation of vascular leakage at the exact location of brain stroke without nonspecific leakage at other intactregions, which show much higher specificity as compared to EB, the widely used method for the BBB damage evaluation.