A Naphthalimide-Based NIR-Emissive AIE Photosensitizer for Synergistic Apoptosis/Ferroptosis-Mediated Antitumor Therapy and Broad-Spectrum Bacterial Inactivation With Rapid Wound Healing.

Abstract

Fluorescence-guided photodynamic therapy (PDT) that targets both malignant cells and pathogenic bacteria is attractive yet challenging, because a single photosensitizer (PS) must combine near-infrared (NIR) emission, efficient reactive oxygen species (ROS) generation, and strong membrane affinity across distinct biological envelopes. Here, we report a donor-π-bridge-engineered series of ionic naphthalimide luminogens, TPA-NIM-M, TPAV-NIM-M, and TPAPV-NIM-M, featuring aggregation-induced emission (AIE) and a cationic membrane-anchoring motif. Among them, TPAPV-NIM-M exhibits far-red/NIR emission, high photostability, and enhanced ROS generation under white-light irradiation through both type I and type II pathways. The extended donor-π conjugation promotes photosensitization, while the ionic amphiphilic structure enables stable plasma membrane (PM) localization, strong membrane binding, and prolonged membrane retention. In cancer cells, photoactivation of TPAPV-NIM-M induces oxidative membrane damage and regulated cell death involving apoptosis and lipid-peroxidation-associated ferroptosis, while allowing real-time fluorescence tracking of membrane blebbing during apoptosis. TPAPV-NIM-M also stains both Gram-negative and Gram-positive bacteria and enables efficient photodynamic bacterial inactivation. In vivo, TPAPV-NIM-M promotes healing in an Escherichia coli-infected wound model and suppresses tumor growth under local light irradiation without apparent systemic toxicity. This work establishes ionic naphthalimide AIEgens as a powerful class of membrane-anchored theranostic agents for image-guided antitumor and antibacterial PDT with broad biomedical potential and translational promise.