Structural remedy toward a next-generation nitrobenzoselenadiazole backbone for enhanced fluorescence and photodynamic therapy

The development of multifunctional fluorophores for simultaneous imaging and therapy has emerged as an important research topic in precision medicine. Nitrobenzoselenadiazole (NBSD), a selenium (Se)-containing dipolar fluorophore with a strong intramolecular charge transfer (ICT), enables both fluorescence imaging and reactive oxygen species (ROS)-mediated photodynamic therapy (PDT). In this study, we introduce a structural optimization strategy to develop NBSD-based derivatives with enhanced optical performance and therapeutic efficacy. Three derivatives, NBSD-Me, NBSD-Cy, and NBSD-Cy-OH, were systematically designed by modifying the electron-donor site to regulate ICT and improve water solubility. Among these, NBSD-Cy-OH exhibited superior fluorescence intensity, photostability in aqueous media, water solubility, and ROS generation under light irradiation. Theoretical calculations further corroborated that NBSD-Cy-OH exhibits the highest intersystem crossing (ISC) rate, supporting its improved PDT efficacy. These findings establish the structural remedy approach as a powerful design principle for developing next-generation theranostic fluorophores.