Rational Synthesis of Imine-Linked Fluorescent Covalent Organic Frameworks with Different pKa for pH Sensing In Vitro and In Vivo

Precise modulation of pH in living cells plays a vital role in the study of many diseases, such as cancer and rheumatoid arthritis. Here, a series of imine-linked covalent organic frameworks (COFs) were rationally designed and developed for pH sensing in tumor cells and zebrafish. Four monomers were chosen to synthesize COFs (COF1-COF4) with different pK(a) by a simple orthogonal combination through condensation reaction. The as-obtained COFs exhibited a sensitive pH-dependent fluorescence response compared to their building blocks. Among them, COF2 possessed a high crystallinity, excellent fluorescence, and suitable pK(a) for biosensing. For bioimaging applications, COF2 was modified with poly-D-lysine (PDL) to improve its biocompatibility and endocytosis efficiency. After that, PDL-modified COF2 (PDL@COF2) was used as a novel fluorescence probe with a superior linear pH response over the range from 5.0 to 8.0 due to its fully reversible protonation and deprotonation. The fluorescent PDL@COF2 was further employed as a good candidate for pH imaging in tumor cells and zebrafish. The as-constructed environment-sensitive fluorescent COFs have greatly expanded the applications of COFs in the biological area.

Automated summary

The study focused on designing a series of COFs for pH sensing in living cells, with COF2 showing high crystallinity and suitable fluorescence properties, providing superior linear pH response in the range from 5.0 to 8.0. The modified PDL@COF2 was successfully used as a fluorescent probe for bioimaging and pH sensing.