DB-PTZ: A Novel NIR-II AIE Photosensitizer for Image-Guided Photothermal and Photodynamic Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and treatment options for advanced disease are still inadequate. Photodynamic therapy (PDT) offers a minimally invasive alternative by generating cytotoxic reactive oxygen species (ROS) upon photosensitizer activation, yet its efficacy is limited by the hypoxic tumor microenvironment. We developed a novel near-infrared II (NIR-II) aggregation-induced emission (AIE) photosensitizer, DB-PTZ, by combining the electron donor phenothiazine with the electron acceptor malononitrile and introducing conjugated peripheral groups to enhance electron delocalization. DB-PTZ nanoparticles, prepared via 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -methoxy (polyethylene glycol)-2000 (DSPE-PEG2000) encapsulation, exhibited uniform size (∼45 nm), negative surface charge (∼35.82 mV), high photothermal conversion efficiency (∼49%), robust stability, minimal hemolysis (