Self-Assembly of a Dual-Targeting and Self-Calibrating Ratiometric Polymer Nanoprobe for Accurate Hypochlorous Acid Imaging

Exploiting an intelligent fluorescent probe, which can precisely target to the lysosome of hepatoma cells and enable accurate molecular imaging, is a key challenge in hepatoma diagnoses. Herein, a single-dye-based polymer nanoprobe (named SPN) with dual-targeting and self-calibrating ratiometric characteristics is rationally fabricated via a simple self-assembly strategy for accurate hypochlorous acid (HClO) imaging in the lysosome of HepG2 cells. Of note, the covalent incorporation of self-calibrating ratiometric fluorophore (pyrene derivatives) into the core of polymer nanoparticles can not only validly avoid the leakage of fluorophores but also greatly enhance their brightness. Besides, this polymer nanoprobe (SPN) displays high water dispersibility, ultrafast response (<1s), favorable selectivity, outstanding long-term stability (>90 days), and good biocompatibility. Furthermore, thanks to the hepatocyte-targeting moiety (galactose) and the interplay of surface charge and size of nanoparticles, the SPN is able to enter into asialoglycoprotein receptor-positive HepG2 cells and further locate at lysosomes, successfully enabling accurate HClO detection in lysosomes of HepG2 cells. This study demonstrates that the versatile SPN can provide more precise dual-targeting and accurate molecular imaging.