Combined Strategies for Optimizing BODIPY-based Near-Infrared Fluorescent Probe Targeting Aβ Oligomers

Recently, some near-infrared fluorescent (NIRF) probes targeting a toxic form of Aβ aggregate, “Aβ oligomer”, have been developed as useful imaging tools in various situations. However, the general strategy for their development has not been established, hampering the appearance of new candidates. In this study, we improved the Aβ oligomer-targeting probe based on a strategic approach. Seven candidates were newly designed by modifying the structure of our previously developed NIRF probe, BAOP-16, according to combined three strategies, and their characteristics were evaluated. The results of computational analysis, photophysical evaluation, and in vitro assays with Aβ species demonstrated that our strategies improved some characteristics of BAOP-16, and a promising candidate, BAOP-24, was successfully developed. Furthermore, the data from in vivo NIRF imaging suggested that BAOP-24 can detect Aβ oligomers in vivo. We believe that insights from this study will help advance the development of imaging probes targeting Aβ oligomers.