Ultra-Bright Heptamethine Dye Clusters Based on a Self-Adaptive Co-Assembly Strategy for NIR-IIb Biomedical Imaging

Abstract

Despite the wide range of applications of bright NIR-II polymethine scaffolds in biomedical imaging, their solvatochromism and aggregation-caused quenching (ACQ) effects in aqueous solutions limit their inherent brightness using traditional encapsulation methods, and effective hydrophilization strategies are still scarce. Here, a new set of Flav dyes is synthesized and PEGylated, followed by manufacturing DSPE@FlavP₂₀₀₀ nanoparticles using a self-adaptive co-assembly strategy to overcome these limitations. FlavP₂₀₀₀ can autonomously adjust its conformation when co-assembled with DSPE-PEG₂₀₀₀ , resulting in high-efficiency luminescence (≈44.9% fluorescence of Flav in DMSO). DSPE@FlavP₂₀₀₀ enables NIR-IIb (>1500 nm) angiography with high signal-to-noise ratios. Notably, this co-assembly can occur in situ between FlavP₂₀₀₀ with proteins in the living body based on a novel mechanism of brightness activation induced by disassembly (BAD), achieving consistent brightness as DSPE@FlavP₂₀₀₀ in blood or serum. The self-adaptive co-assembly strategy can be enhanced by incorporating an IPA moiety, which dynamically binds to albumin to prolong the dye's blood circulation time. Thus, the "enhanced" BAD is successfully applied to long-term vascular imaging and sciatic nerve imaging. Both the self-adaptive co-assembly strategy and BAD phenomenon improve the selectivity and availability of the hydrophilization methods, paving the way for efficient biological applications of polymethine dyes.

Keywords: Flav cyanine dyes; NIR-IIb bioimaging; disassembly of dye aggregation; remarkable brightness activation; self-adaptive co-assembly.