Oxygen-Embedded Fused-Ring Structure for NIR-Triggered Multimodal Phototherapy of Laryngeal Cancer.

Laryngeal cancer requires precise and minimally invasive therapeutic strategies to preserve critical physiological functions. Herein, an oxygen-embedded fused-ring organic semiconductor (COi8FIC) was reported, which is formulated into multifunctional nanoparticles for near-infrared (NIR)-triggered multimodal phototherapy. The incorporation of oxygen atoms into the conjugated backbone, together with fluorinated cyanoindanone end-groups, narrows the bandgap to 1.35 eV and enhances intramolecular charge transfer, thereby promoting non-radiative decay and intersystem crossing. As a result, COi8FIC nanoparticles exhibit a high photothermal conversion efficiency of 62% and generate multiple reactive oxygen species (•OH, O2-, and 1O2) via synergistic Type I and Type II photodynamic pathways. In vitro, the nanoparticles produce approximately 2.5-fold higher ROS levels than monotherapies. In vivo, NIR irradiation induces rapid hyperthermia (ΔT ca. 23.6 °C), resulting in a tumor growth inhibition rate of 93.3%. Tumor regression was observed in all treated mice, with complete tumor eradication in three of five mice and near-complete elimination in the remaining two, with no significant irreversible organ damage. These results highlight the potential of this system as a promising platform for multimodal phototherapy of laryngeal cancer.