A ClO--responsive porphyrin prodrug for fluorescence imaging and combined chemo-photodynamic treatment of hepatocellular carcinoma cells.
TL;DR
POR-CA was supported as an in vitro proof-of-concept platform integrating ClO--responsive fluorescence-quenching sensing with light-dependent phototoxicity, while the contribution of the released cinnamic-acid-derived component remained to be established.
Abstract
The hypoxic tumor microenvironment (TME) of hepatocellular carcinoma (HCC) featured overexpressed hypochlorite (ClO-), which represented both a biochemical hallmark and a potential therapeutic trigger. Herein, POR-CA, a near-infrared (NIR) activatable prodrug constructed by conjugating cinnamic acid to a 4-(4-aminophenyl) porphyrin fluorophore, was reported. Exposure to ClO- produced a concentration-dependent decrease in near-infrared fluorescence, enabling fluorescence-quenching sensing under the tested conditions. Spectroscopic characterization confirmed rapid and sensitive ClO- responsiveness with favorable pH stability. Notably, the porphyrin backbone acted as an intrinsic photosensitizer to generate reactive oxygen species (ROS) under 660 nm laser irradiation for photodynamic therapy (PDT). HRMS provided evidence consistent with ClO--induced cleavage and formation of a TAPP-related fragment. POR-CA exhibited differential dark cytotoxicity in HepG-2 and LO-2 cells and light-dependent phototoxicity under the tested conditions. These results supported POR-CA as an in vitro proof-of-concept platform integrating ClO--responsive fluorescence-quenching sensing with light-dependent phototoxicity, while the contribution of the released cinnamic-acid-derived component remained to be established. Nonetheless, this molecular design perspective served as a valuable reference for subsequent translational optimization.