Synthesis and Self-Assembly Behavior of Chlorophyll Derivatives for Ratiometric Photoacoustic Signal Optimization

Self-assembly provides researchers powerful tools for creating ordered functional structures and complex architectures. Investigation of in vivo self-assembly reveals the assembly/aggregation-induced retention (AIR) effect and enhanced targeting effect, which can be applied to promising biomedical applications by enhancing molecular accumulation in the target region. These unique bioeffects inspire the interest of researchers in construction of self-assembled nanomaterials in biological systems. Although many efforts have been achieved, the in-depth analysis of the relationship between assemblies and functions is rarely reported. Here, we focus on the relationship of chlorophyll-derivative assemblies and their photoacoustic signals and attempt to establish a method for monitoring the aggregation efficiency in vivo based on photoacoustic signals. Three arginine-rich peptide-purpurin molecules were designed and synthesized. The assembled capabilities and assembly processes of these molecules were characterized and monitored by UV, fluorescence, and CD spectra images of gradually changing polarities in mixed solvents, and the morphologies of the assemblies were observed by TEM. Furthermore, the relationship between the aggregation ratios of the molecules and the ratiometric photoacoustic signals was systemically studied. We prospect that the fundamental research in revealing objective laws will be useful for future guidance in optimizing photoacoustic detection windows and assembled molecule design.